Stimulus Substitution Research Articles

Sleep should not be this difficult: An interpretive descriptive study of older adults' perspectives on behaviour change elements in Sleepwell and experiences with benzodiazepine discontinuation

SummaryBenzodiazepine receptor agonists are often used for insomnia in older adults contrary to current evidence. The harms outweigh the benefits, which are limited. Cognitive behavioural therapy for insomnia is the first‐line recommended treatment. Sleepwell was created as a repository of evidence‐based resources to promote cognitive behavioural therapy for insomnia and limit benzodiazepine receptor agonist use. This qualitative study uses an interpretive description design and reflexive thematic analysis to explore older adults' perspectives on behavioural change techniques used in Sleepwell resources. It also explores challenges and opportunities towards benzodiazepine receptor agonist discontinuation and cognitive behavioural therapy for insomnia use. Participants were recruited from the Sleepwell arm of a randomized controlled trial. Data were collected from 15 older adults using semi‐structured interviews. Two main themes were developed: (1) sleep should not be this difficult; and (2) whether you know it, or learn it, drugs are bad. Two sub‐themes were created within the first theme: (1) justification of benzodiazepine receptor agonist use to achieve sleep goals; (2) efforts of committing to cognitive behavioural therapy for insomnia. Several behavioural change techniques (e.g. information about consequences, anticipated regret, salience of consequences) were enablers of benzodiazepine receptor agonist‐related behaviour change. For committing to cognitive behavioural therapy for insomnia, several behavioural change techniques (e.g. self‐monitoring of behaviour, distraction, stimulus substitution) were beneficial, but social support, which was perceived as useful, was absent. Older adults experienced tension with benzodiazepine receptor agonist use and deprescribing, despite knowing or learning the potential consequences of benzodiazepine receptor agonists. Cognitive behavioural therapy for insomnia implementation was challenging. Embedded behavioural change techniques in the Sleepwell booklets were identified as helpful, but more (e.g. social support) are needed to optimize cognitive behavioural therapy for insomnia use.

A Review of Backward Higher-Order Conditioning: Implications for a Pavlovian Conditioning Analysis of Stimulus Equivalence.

Stimulus equivalence (SE) is demonstrated when participants exposed to conditional discrimination training pass tests for reflexivity, symmetry, transitivity, and equivalence (symmetry combined with transitivity). Most theorists attribute the origin of SE to operant processes, but some argue that it results from Pavlovian conditioning. Symmetry is problematic for the latter hypothesis because it seems to require excitatory backward conditioning. However, equivalence tests resemble backward sensory preconditioning (BSP) and backward second-order conditioning (BSOC), two well-established processes. A review of associationistic theories of BSP and BSOC showed that the temporal coding hypothesis (TCH) explains outcomes that other associationistic theories cannot explain (i.e., BSOC and BSP effects after first-order conditioning with delay vs. trace conditioning and forward vs. backward conditioning). The TCH assumes that organisms encode the temporal attributes of stimulus events (e.g., order and interval duration) and this temporal information is integrated across separate phases of training. The TCH seems compatible with a behavioral analysis if direct stimulus control replaces the notion of temporal maps. The TCH perspective does not seem applicable to SE because SE tests are not predictive tasks. This suggests that SE is fundamentally different from BSP and BSOC and a Pavlovian conditioning analysis of SE is inadequate. This conclusion is consistent with previous criticism of a Pavlovian account of SE according to which Pavlovian conditioning cannot be interpreted as stimulus substitution.

Characterization of 3,4-methylenedioxypyrovalerone discrimination in female Sprague-Dawley rats.

3,4-Methylenedioxypyrovalerone (MDPV), one of several synthetic cathinones, is a popular constituent of illicit 'bath salts'. In preclinical studies utilizing drug discrimination methods with male rodents, MDPV has been characterized as similar to both cocaine and 3,4-methylenedioxymethamphetamine-hydrochloride (MDMA). Whereas few drug discrimination studies have utilized female rats, the current study evaluated the discriminative stimulus effects of MDPV in 12 adult female Sprague-Dawley rats trained to discriminate 0.5 mg/kg MDPV from saline under a fixed ratio 20 schedule of food reinforcement. Stimulus substitution was assessed with MDPV and its enantiomers, other synthetic cathinones [alpha pyrrolidinopentiophenone-hydrochloride(α-PVP), 4-methylmethcathinone (4-MMC)], other dopamine agonists (cocaine, [+)-methamphetamine] and serotonin agonists [MDMA, lysergic acid diethylamide (LSD)] Stimulus antagonism was assessed with the dopamine D1 receptor antagonist, Sch 23390 and the D2 receptor antagonist, haloperidol. Cocaine and (+)-methamphetamine engendered full stimulus generalization to MDPV with minimal effects on response rate. LSD produced partial substitution, whereas MDMA and 4-MMC produced complete substitution, and all these serotonergic compounds produced dose-dependent response suppression. (S)-MDPV and α-PVP engendered full substitution with similar potency to the racemate, while (R)-MDPV failed to substitute up to 5 mg/kg. Both Sch 23390 and haloperidol attenuated the discrimination of low MDPV doses and essentially shifted the dose-response curve to the right but failed to block discrimination of the training dose. These findings are generally consistent with previous reports based exclusively on male rodents. Moreover, they confirm the contribution of dopaminergic mechanisms but do not rule out the possible contribution of other neurotransmitter actions to the interoceptive stimulus effects of MDPV.

Sensory stimulation in the treatment of children with sleep-related rhythmic movement disorder: a feasibility and acceptability study

BackgroundSleep-related rhythmic movement disorder is characterized by repetitive gross-motor movements at sleep onset or during sleep, which result in clinical consequences such as impact on daytime functioning and injury. No well-established therapies exist today. Substituting the patient’s movements with external sensory stimulation may offer a treatment modality. The aim of the current study was to test the feasibility and acceptability of vestibular stimulation using a rocking bed (Somnomat) in children with rhythmic movement disorder and to assess children’s movement preference.MethodsChildren with rhythmic movement disorder (n = 6, Age: 5–14 years) were studied over three nights in a sleep laboratory: adaptation night (normal bed) and randomised-order baseline (Somnomat) and intervention nights (Somnomat). Child’s preferred movement direction (head-to-toe or side-to-side) and frequency (between 0.25 and 2 Hz), determined during an afternoon protocol, were applied using the Somnomat for 1 h after lights out, and in response to subsequent episodes of rhythmic movement during intervention nights. Comfort assessed using a questionnaire, and objective sleep parameters assessed using videosomnography, were compared.ResultsThe participants’ sometimes violent rhythmic movements did not disturb device performance. All children rated intervention nights equally or more comfortable than baseline nights. Self-reported sleep quality, as well as the number and duration of movement episodes did not significantly differ between baseline and intervention nights.ConclusionsProviding rocking movements using the Somnomat is both technically feasible and acceptable to the target population. The therapeutic value of this novel stimulus substitution for rhythmic movement disorder should now be evaluated in a larger sample over a longer period in the home setting.Trial registrationThe trial was retrospectively registered at clinicaltrials.gov (NCT03528096) on May 17th 2018.

Superstition revisited: Sex, species, and adventitious reinforcement

Skinner’s (1948) ‘Superstition’ in the Pigeon paper proposed that accidental response-reward contingencies, via adventitious reinforcement, could operantly condition the behaviors of pigeons under fixed-time (response-independent) schedules of food delivery. Skinner likened the behavior of pigeons under these fixed-time schedules to the superstitious behavior of humans and proposed that both response patterns were the result of contiguous pairings of rewards following some response. Alternative explanations of superstitious behavior have included Staddon and Simmelhag’s (1971) stimulus substitution account and Timberlake and Lucas’s (1985) elicited species-typical appetitive behavior account. Under both these alternative explanations of superstitious behavior, observations of pigeons under fixed-time schedules revealed a lack of idiosyncratic responding, which is a critical element in Skinner’s explanation of superstitious behavior via adventitious reinforcement. The following study implemented 4 fixed-time schedule experiments to further study superstition. In Experiment 1, male and female pigeons were compared, which provided support for the disparity in response patterns observed in previous studies. Experiments 2–4 examined the behavior of roller pigeons, ring-necked doves, and bantam chickens. In all the above studies, a lack of idiosyncratic responding and emergence of species-typical foraging behavior was observed. The results provide additional evidence that the ‘superstitious’ behavior that emerges in pigeons and other organisms under response-independent food schedules is the result of elicited species-typical food getting behaviors, and that these behaviors emerge as a result of frequent food deliveries in environments that support such foraging repertoires.

Sound Affects the Discrimination of Low Light Intensities in the Rabbit Visual Cortex

Visual evoked potentials (VEP) recorded from the visual cortex of conscious rabbits in chronic experiments were used to study the effects of sound (2000 Hz, 70 dB, 40 msec) on the discrimination of low light intensities (0.3–1 cd/m2). Sounds were delivered with different time delays before and after replacement of one light intensity by another (range –750 to +150 msec). The sound itself did not induce any response. A total of 42 experiments on three rabbits showed that sound had a significant modulatory effect on the discrimination of low light intensities in the range of sound-light intervals from –300 to +50 msec. Sound had the strongest effect going from high light intensities (1 cd/m2) to low (0.3 cd/m2). Analysis of the phases of visual evoked potentials showed that sound had a significant influence on the light response at intervals of –300, –100, –60, –40, –20, 0, +20, and +50 msec. During the P2 phase (120–150 msec from the moment of light stimulus substitution), sound had its greatest influence on substitution of low light intensities both in terms of the number of time intervals (seven) at which the effect of sound was significant (p < 0.05) and in terms of the extent of the effect of sound on the light response. The effects of sound in the P2 phase were almost exclusively facilitatory – by 19–36% compared with responses to light, while the N1 (80–110 msec) and N2 (180–250 msec) phases included 2–3 intervals with significant sound effects, the extent of facilitation of the response to light varying over the range 8–12%. It is suggested that the action of sound on the light response over time is mediated in the visual cortex with some delay due to passage of the sound signal through the auditory cortex, parietal cortex, and superior colliculi.

Specific Modulation by Sound of Primary Visual Cortex Neuron Responses to Light Stimuli of Different Intensities in Rabbits

Experiments were performed on four European rabbits (Orictolagus cuniculus) and included extracellular recordings of a total of 92 neurons. The first series of experiments recorded the responses of 63 neurons to substitution of visual stimuli presented in pairs (pairs with intensities of 0.28 and 1; 1 and 3; 3 and 6; 6 and 8.5; 8.5 and 14; 14 and 17; and 17 and 20 cd/m2). The same stimulus substitutions were then presented with sound (70 dB, 2000 Hz, 40 msec). Neurons did not respond directly to the sound. Two groups of neurons were found. Responses to “light + sound” complexes (in the interval 40–100 msec from the moment of stimulus substitution) increased by a mean 41% (p < 0.0001) at the lowest stimulus intensities in neurons of group 1 (31%). As light intensity increased, discharges in response to the complex decreased to or even below the level of responses to light. Neurons of group 2 (19%) showed the opposite properties: at low light intensities, responses to complexes were comparable with or even smaller than responses to light, while at high intensities (14–20 cd/m2) responses were significantly different (p < 0.05) from responses to light (by 20–39%). The next series of experiments reconstructed the sensory vector spaces on the basis of the responses to 29 neurons to light stimuli of eight different intensities and “sound + light” complexes. Sound was also found to have a double action on the sensory spaces of complexes. Some neurons showed marked increases in the angular distance between the two lowest-intensity stimuli (0.28 and 1 cd/m2), while others showed an increase in the angular distance for the highest intensities. These changes in the structure of the spaces were consisted with the neuron groups identified in the first two series. Comparison of the dynamics of neuron responses and the amplitudes of evoked potentials in the same stimulation conditions showed that there was significant similarity. Thus, these data lead to the conclusion that modulation of visual cortex neuron activity by sound occurs in a complex, nonlinear manner.

Avoidance but not aversion following sensory preconditioning with flavors: A challenge to stimulus substitution.

After two neutral stimuli have been paired (AB), directly conditioning a response to one of them (A) will also be reflected in a change in responding to the other (B). Standard accounts of this sensory preconditioning effect assume that it is mediated by a memory involving the stimulus that was directly conditioned (i.e., A). The reliance on this shared pathway implies that sensory preconditioning (involving B) and direct conditioning (involving A) should support qualitatively similar patterns of responding. In three experiments, directly pairing A with lithium chloride (LiCl) delivery resulted in both a reduction in consumption of A (i.e., avoidance) and a reduction in the size of licking clusters it elicits (i.e., aversion). In contrast, the sensory preconditioning effect resulted in a reduction in the consumption of B but no change in the nature of the licking response that it elicited; and a similar dissociation was observed after trace conditioning. These dissociations involving direct conditioning and sensory preconditioning, observed over a range of flavor concentrations and different doses of LiCl, undermine standard accounts of sensory preconditioning that are based on the assumption of stimulus substitution.

Supplemental Material for Avoidance but Not Aversion Following Sensory Preconditioning With Flavors: A Challenge to Stimulus Substitution

Supplemental Material for Avoidance but Not Aversion Following Sensory Preconditioning With Flavors: A Challenge to Stimulus Substitution

Disentangling the nature of the nicotine stimulus.

Learning involving interoceptive stimuli likely plays an important role in many diseases and psychopathologies. Within this area, there has been extensive research investigating the interoceptive stimulus effects of abused drugs. In this pursuit, behavioral pharmacologists have taken advantage of what is known about learning processes and adapted the techniques to investigate the behavioral and receptor mechanisms of drug stimuli. Of particular interest is the nicotine stimulus and the use of the two-lever operant drug discrimination task and the Pavlovian drug discriminated goal-tracking task. There is strong concordance between the two methods when using "standard" testing protocols that minimize learning on test days. For example, ABT-418, nornicotine, and varenicline all fully evoked nicotine-appropriate responding. Notably, research from our laboratory with the discriminated goal-tracking task has used an alternative testing protocol. This protocol assesses stimulus substitution based on how well extinction learning using a non-nicotine ligand transfers back to the nicotine stimulus. These findings challenge conclusions based on more "standard" testing procedures (e.g., ABT-418 is not nicotine-like). As a starting point, we propose Thurstone scaling as a quantitative method for more precisely comparing transfer of extinction across doses, experiments, and investigators. We close with a discussion of future research directions and potential implications of the research for understanding interoceptive stimuli.

Responses of Rabbit Visual Cortex Neurons to Changes in the Orientation and Intensity of Visual Stimuli

We report here studies of changes in the numbers of spikes in the early phasic discharges (50–90 msec from the moment of stimulus substitution) of neurons in the primary visual cortex of conscious rabbits in response to substitution of lines of different orientations (0–90°) but flashing at constant intensity on a screen, to substitution of lines of constant orientation but different intensities, and to substitutions of complex stimuli in which simultaneous changes were made to the orientation and intensity. Factor analysis of the results showed that the number of spikes in the early phasic discharges of some neurons allowed the two-dimensional sensory space of orientations to be reconstructed. This space was identified in 13 of the 43 neurons studied (30%). Five of the 30 cells studied (16.7%) showed both two-dimensional orientation sensory spaces and two-dimensional intensity spaces. Achromatic spaces were reconstructed by substituting lines of different intensity but constant orientation. On substitution of complex stimuli (intensity + orientation), four stimuli with initial orientations of 0–38.58° (0° corresponding to a vertical line) had an intensity of 5 cd/m2, while the other four stimuli (with orientations of 51.44–90°) were presented at an intensity of 15 cd/m2. On the plane of the sensory space formed by the first two significant factors, the two groups of stimuli with different intensities were located in opposite quadrants of a circle, while within the groups the stimuli were ordered in a sequence close to the order of increases in their slope angles, from smaller angles to greater. It is suggested that in this version, a single sensory plane space reflects the interaction between the orientation and intensity attributes of the visual stimulus, the intensity factor being predominant. A total of seven such cells were found among the 57 studied (12%).

Dopamine release during reinforcement learning

Event Abstract Back to Event Dopamine release during reinforcement learning Paul Phillips1*, Jeremy J. Clark1 and Andrew Hart1 1 University of Washington, Departments of Psychiatry & Behavioral Sciences and Pharmacology, United States Animals adapt their behavior to changing environments by learning associations between reinforcers (i.e. food and water) and stimuli that signal their availability. Appetitive classical conditioning is one of the most fundamental processes for such behavioral adaptation. Indeed, this form of reinforcement learning provides organisms with the predictive information needed for the preparatory action necessary to maximize reward. Computational approaches to learning, motivated in part by the Rescorla-Wagner learning rule, stress that learning should occur only in circumstances where a particular outcome deviates from an expected outcome (a prediction error). In the Rescorla-Wagner model, value is assigned to reward-predicting stimuli which is stored and updated when prediction errors occur. Accordingly, behavioral studies indicate that under many conditions, reward-predicting stimuli acquire incentive value similar to appetitive unconditioned stimuli through stimulus substitution as evidenced by conditioned approach and conditioned reinforcement.A formal role of dopamine in reinforcement learning comes from electrophysiological studies examining the firing patterns of the dopamine neurons of the ventral tegmental area and substantia nigra during the presentation of conditioned and unconditioned stimuli. These studies indicate that transient increases in dopamine neuron firing rates, which are thought to produce rapid and phasic elevations in extracellular dopamine concentration throughout the striatum, encode the discrepancy between expected and actual reward outcomes consistent with a prediction error signal that favors learning.Using fast-scan cyclic voltammetry at microelectrodes chronically implanted in the striatum, we are able to detect dopamine release with subsecond resolution over multiple days of learning paradigms in rodents. This approach allows us to compare dopamine release profiles between areas of the striatum throughout learning of the association of environmental stimuli with either deterministic or probabilistic reward contingencies; and to examine these patterns across individual variation in the learning strategies that animals adopt. Conference: 41st European Brain and Behaviour Society Meeting, Rhodes Island, Greece, 13 Sep - 18 Sep, 2009. Presentation Type: Oral Presentation Topic: Symposia lectures Citation: Phillips P, Clark JJ and Hart A (2009). Dopamine release during reinforcement learning. Conference Abstract: 41st European Brain and Behaviour Society Meeting. doi: 10.3389/conf.neuro.08.2009.09.042 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 04 Jun 2009; Published Online: 04 Jun 2009. * Correspondence: Paul Phillips, University of Washington, Departments of Psychiatry & Behavioral Sciences and Pharmacology, Seattle, United States, pemp@u.washington.edu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Paul Phillips Jeremy J Clark Andrew Hart Google Paul Phillips Jeremy J Clark Andrew Hart Google Scholar Paul Phillips Jeremy J Clark Andrew Hart PubMed Paul Phillips Jeremy J Clark Andrew Hart Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Assessment of brightness and color differences by neurons in the superior colliculus of the rabbit

The responses of 83 neurons in the rabbit superior colliculus to substitution of color stimuli of different brightnesses and black-and-white stimuli of different intensities were studied. Superior colliculus neurons were found to respond with initial and late phasic discharges (over the periods 50-90 msec and 120-300 msec from the moment of stimulus substitution respectively), along with prolonged tonic discharges whose spike frequencies depended on the intensity of the stimulus. Analysis of the phasic responses of the neurons allowed three groups of cells to be identified. One group of cells (25 of the cells studied, 30%), identified on the basis of early neuron responses, were specialized for detecting brightness differences between black-and-white and color stimuli of different intensities. The sensory spaces reconstructed on the basis of spike discharge frequencies in the early discharges of these neurons were achromatic and two-dimensional. Another group of neurons (16 of the cells studied, 19%) were mainly identified on analysis of late phasic discharges and had four-dimensional spaces with two color and two achromatic axes. The third group of cells (four neurons, 5%) had early discharges with two-dimensional achromatic sensory spaces and late discharges with four-dimensional spaces. It is suggested that reconstruction of the four-dimensional space requires processing of information from the visual cortex on color and intensity differences between stimuli. The sensory spaces of superior colliculus neurons reconstructed on the basis of phasic discharges essentially coincided with the sensory spaces of neurons in the visual cortex and lateral geniculate body and spaces obtained by analysis of the N85 component of visual evoked potentials in rabbits recorded using similar stimulation. This may support the vector coding principle in the visual analyzer.

Computation of color and brightness differences by neurons in the lateral geniculate nucleus of the rabbit

The responses of 51 neurons in the lateral geniculate nucleus of the rabbit to substitution of colored stimuli different brightness and stimuli differing only in intensity were studied. Neurons in the geniculate nucleus, like neurons in the visual cortex, were found to respond with initial phasic discharges at 50-90 msec after stimulus substitution, the magnitudes of these responses correlating with the interstimulus differences; neurons also showed prolonged tonic responses in which the spike frequency depended on the intensity of the stimulus presented. Analysis of phasic responses allowed two groups of neurons to be identified: some were specialized to discriminate stimulus intensity only, while others were specialized to discriminate both the intensity and the color tone of the stimulus. Use of the magnitude of the early phasic discharge as a measure of the difference between stimuli yielded a sensory space for lateral geniculate nucleus neurons. The responses of neurons in the first group (44 cells, 86%) produced a two-dimensional achromatic space with two axes--brightness and darkness; this structure appeared independently of whether stimuli were of the same or different color tones. The phasic responses of neurons in the second group (seven of 51, 14%) generated a four-dimensional space with two color and two achromatic axes. The color and achromatic spaces of lateral geniculate nucleus neurons were analogous to the spaces previously identified for neurons in the rabbit visual cortex using the same stimulation conditions. The sensory spaces reconstructed on the basis of neuron phasic discharges essentially coincided with the spaces obtained from analysis of the N85 component of visual evoked potentials in rabbits, which provides support for the vector information coding principle in the visual analyzer. The tonic discharges of most lateral geniculate nucleus neurons correlated linearly with changes in stimulus intensity and can be regarded as reflecting a pre-detector function for the visual cortex detector neurons.

Ligands selective for α4β2 but not α3β4 or α7 nicotinic receptors generalise to the nicotine discriminative stimulus in the rat

Nicotine produces behavioural effects that are potentially related to its interaction with diverse nicotinic acetylcholine receptor populations. Evidence from gene deletion studies suggests that the interoceptive stimulus properties of nicotine are mediated by heteromeric high-affinity receptors containing alpha4beta2 subunits. Mice lacking beta2 subunits do not discriminate nicotine (Shoaib et al., Neuropharmacology, 42:530-539, 2002), and nicotine does not elicit dopamine release in these animals (Grady et al., J Neurochem, 76:258-268, 2001). The stimulus properties of nicotine can be detected in rats using a two-lever operant drug discrimination paradigm, allowing them to be classified pharmacologically using ligands with selectivity for receptors containing alpha4beta2, alpha3beta4 or alpha7 subunits. Rats trained to discriminate 0.4 mg/kg nicotine from vehicle were given the nicotinic receptor agonists, cytisine, varenicline, TC2559, ABT-594, A-85380 (all having high affinity but varying selectivity for alpha4beta2-containing receptors), and WO 03/062224 and WO 01/60821A1 (selective for beta4- and alpha7-containing receptors, respectively). In separate studies, WO 03/062224 was used as the training stimulus. Nicotine, TC-2559, A-85380 and ABT-594 showed dose-dependent and complete stimulus substitution, whilst WO 03/062224 and WO 01/60821A1 were completely without effect. Cytisine and varenicline showed partial generalisation, consistent with their partial agonist activity at nicotinic receptors eliciting dopamine release in rat striatal slices. After almost 50 training sessions with WO 03/062224, there was no clear evidence that an alpha3beta4 receptor agonist could sustain a discriminable stimulus. Substitution to the nicotine discriminative stimulus required high-affinity and high intrinsic activity at beta2 but not at beta4- or at alpha7-containing nicotinic receptors.

Comparison of the discriminative stimulus effects of 3,4-methylenedioxymethamphetamine (MDMA) and cocaine: asymmetric generalization

Evidence suggests that (±)3,4-methylenedioxymethamphetamine (MDMA) and psychostimulants produce similar but non-identical stimulus effects in animals. To examine this hypothesis, groups of rats were trained to discriminate either MDMA (1.5 mg/kg) or cocaine (8 mg/kg) from saline vehicle using a two-lever operant procedure under a variable interval (VI) 15 s schedule of reinforcement. Once the animals were trained, tests of stimulus generalization were conducted with (±)MDMA, cocaine, S(+)MDMA, and R(−)MDMA. As previously demonstrated, both S(+)MDMA and R(−)MDMA (ED 50=0.8 and 1.2 mg/kg, respectively) substituted for (±)MDMA. Stimulus generalization also occurred upon administration of cocaine (ED 50=4.6 mg/kg) to the (±)MDMA-trained animals. In the cocaine-trained animals, however, stimulus generalization did not occur to (±)MDMA, S(+)MDMA nor R(−)MDMA. Receptor binding profiles for MDMA and cocaine were compared in an effort to identify any novel and common receptor-based mechanism(s) to explain stimulus generalization of MDMA-trained animals to the effects of cocaine, but only their actions on neurotransmitter transporters seem applicable. Taken together, the results indicate that stimulus substitution between MDMA and cocaine is asymmetric and suggest that although similarities exist between the stimulus actions of MDMA and cocaine, differences might be explained by their differential effects on increasing synaptic concentrations of serotonin (5-HT), dopamine (DA), and/or norepinephrine (NE).

Role of Acetaldehyde in the Discriminative Stimulus Effects of Ethanol

Acetaldehyde has been suggested to mediate some of the effects of ethanol. Acetaldehyde can be produced by the enzyme catalase within the brain after ethanol administration. The catalase inhibitor 3-amino-1,2,4-triazole (AT) reduces the production of acetaldehyde, and AT administration can reduce a number of ethanol-induced behavioral effects; this suggests the involvement of acetaldehyde in these behaviors. However, a role for acetaldehyde in mediating the discriminative stimulus effects of ethanol remains unclear. The contribution of acetaldehyde to the discriminative stimulus effects of ethanol was investigated by use of a two-lever drug discrimination paradigm with food reinforcement. Male Long-Evans rats were trained to discriminate water from either 1.0 or 2.0 g/kg ethanol. Stimulus substitution tests were conducted with ethanol (0-2.5 g/kg by gavage) and acetaldehyde (0-300 mg/kg intraperitoneally). A cumulative dose-response procedure was then used to investigate the effects of pretreatments with AT (0.5 and 1.0 g/kg intraperitoneally) on ethanol discrimination. Acetaldehyde up to doses that decreased response rates (300 mg/kg) did not substitute for the discriminative stimulus effects of 1.0 or 2.0 g/kg ethanol. In addition, AT pretreatment did not affect the dose-response curves for ethanol discrimination. These results show that exogenous acetaldehyde administration does not produce discriminative stimulus effects that are similar to those of ethanol. Also, pretreatment with the catalase inhibitor did not affect the dose-response curve for ethanol discrimination, and this suggests that endogenously produced acetaldehyde does not contribute to the discriminative stimulus effects of ethanol. Together these results suggest that acetaldehyde does not mediate the discriminative stimulus effects of 1.0 to 2.0 g/kg ethanol.

Net Amount of Food Affects Autoshaped Response Rate, Response Latency, and Gape Amplitude in Pigeons

The contribution of net amount of food to conditioned response strength and topography was assessed in four pigeons under autoshaping contingencies. In each session, under one baseline phase and three replication phases, three trial types were presented sequentially: One conditioned stimulus (keylight) signaled one small pellet, another signaled one large pellet, and a third signaled seven small pellets which were weight-matched to one large pellet. Five dependent variables were response rates and latencies based on the occurrence of both keyswitch closures and gapes (beak openings) and gape amplitudes. In result, net amount of food, not pellet diameter or number, affected all dependent variables. Notably, gape amplitudes elicited by the seven-small pellet keylights were larger than the gape amplutides elicited by the one-small pellet keylights even though the gape amplitudes elicited by both unconditioned stimuli (one or seven pellets) were equally small. This mismatch between conditioned and unconditioned responses is incompatible with stimulus substitution accounts but is compatible with an associative strength account. Furthermore, the changes in the dependent variables were most likely determined by Pavlovian and not by inadvertent operant contingencies. The findings demonstrate that an analysis of classical conditioning benefits from the inclusion of topographical measures.

Taste preference synergy between glutamate receptor agonists and inosine monophosphate in rats.

Monosodium glutamate (MSG) elicits a taste called umami and interacts synergistically with nucleotide monophosphates such as 5'-inosine monophosphate (IMP) to potentiate this taste intensity. Indeed, the synergistic interaction of nucleotide monophosphates and MSG is a hallmark of umami. We examined interactions between MSG and other taste stimuli, including IMP, by measuring the lick rates of non-deprived rats during 30 s trials. To control for non-linear psychophysical functions, the concentration of one taste stimulus in a binary mixture was systematically increased while the concentration of the second taste stimulus was decreased (stimulus substitution method). Synergy between two stimuli was detected if the lick rate for a binary mixture exceeded that expected from the sum of the lick rates for each stimulus alone. In initial experiments, taste synergy was observed when rats were presented with mixtures of MSG and IMP but not with mixtures of MSG and sucrose. In subsequent experiments, glutamate receptor agonists other than MSG were presented with IMP to test for taste synergy. No evidence of synergy was seen when rats were presented with mixtures of IMP and kainic acid or IMP and N:-methyl-D-aspartate. However, taste synergy between IMP and L-AP4, a potent agonist at mGluR4 receptors, was observed. These results suggest that a metabotropic glutamate receptor similar to mGluR4 may be involved in the taste synergy that characterizes umami.

How the Challenge of Explaining Learning Influenced the Origins and Development of John B. Watson's Behaviorism

Before he invented behaviorism, John B. Watson considered learning one of the most important topics in psychology. Watson conducted excellent empirical research on animal learning. He developed behaviorism in part to promote research and elevate the status of learning in psychology. Watson was much less successful in the adequacy and originality of the mechanisms he proposed to explain learning. By assimilating the method of classical conditioning and adopting Pavlov's theory of stimulus substitution, Watson linked behaviorism with a new method that could compete with both Titchener's method of introspection and Freud's methods of psychoanalysis. Watson's interest in explaining psychopathology led to the discovery of conditioned emotional responses and a behavioristic explanation for the learning of phobic behavior. Watson established learning as a central topic for basic research and application in American psychology.