Magazine Entries Research Articles

Repeated Δ-9-Tetrahydrocannabinol administration dose dependently increases stablished schedule-induced drinking

RationaleSchedule-induced drinking (SID) reproduces an excessive and repetitive behavioural pattern that has led to propose this procedure as an animal model to study compulsive behaviours. Although it is known that cannabis can cause several adverse effects, in recent years there has been great interest in the medical application of cannabis derivatives for obsessive-compulsive related disorders.ObjectivesThe present study investigated the effects of repeated THC administration on rates of previously acquired SID, as well as the possible alteration of its temporal distribution along inter-food intervals.MethodsMale Wistar rats acquired SID under a 30 min fixed-time 30-sec food delivery schedule (from 30 to 43 sessions to reach a stable level). Thereafter, 5 or 10 mg/kg daily i.p. injections of THC or vehicle were repeatedly administered for 7 days to evaluate the effects on SID.ResultsRepeated THC administration at a dose of 5 mg/kg resulted in an increase on licking. Surprisingly, no effects on SID were observed with the 10 mg/kg dose. However, magazine entries were reduced with both THC doses. THC also modified the temporal distributions of licking and magazine entries during inter-food intervals.ConclusionsThe present results show that repeated THC administration may (i) increase induced licking at moderate doses, (ii) reduce magazine entries, and (iii) affect the temporal pattern of SID. These findings suggest that THC does not appear to be beneficial to reduce compulsive behaviour in this animal model, while another collateral effect of THC —such as a greater habitual-like behaviour— needs to be considered.

A History of Low-Dose Ethanol Shifts the Role of Ventral Hippocampus during Reward Seeking in Male Mice.

Although casual drinkers are a majority of the alcohol drinking population, understanding of the long-term effects of chronic exposure to lower levels of alcohol is limited. Chronic exposure to lower doses of ethanol may facilitate the development of alcohol use disorders, potentially because of ethanol effects on reward learning and motivation. Indeed, our previously published findings showed that chronic low-dose ethanol exposure enhanced motivation for sucrose in male, but not female, mice. As the ventral hippocampus (vHPC) is sensitive to disruption by higher doses of chronic ethanol and tracks reward-related information, we hypothesized that this region is impacted by low-dose ethanol and, further, that manipulating vHPC activity would alter reward motivation. In vivo electrophysiological recordings of vHPC population neural activity during progressive ratio testing revealed that vHPC activity was suppressed in the period immediately after reward seeking (lever press) in ethanol-naive controls, whereas suppression of vHPC activity anticipated reward seeking in ethanol-exposed mice. In both ethanol-naive and exposed mice, vHPC activity was suppressed before a reward magazine entry. Temporally selective inhibition of vHPC using optogenetics increased motivation for sucrose in ethanol-naive controls, but not in ethanol-exposed mice. Further, regardless of exposure history, vHPC inhibition promoted checking of the reward magazine, indicating a role for vHPC in reward tracking. There was no effect of chemogenetic inhibition of the vHPC either during training or testing on sucrose reward motivation. These results reveal novel ethanol-induced alterations in vHPC neural activity that shift how vHPC activity is able to regulate reward seeking.

Slow-rising and fast-falling dopaminergic dynamics jointly adjust negative prediction error in the ventral striatum.

The greater the reward expectations are, the more different the brain's physiological response will be. Although it is well-documented that better-than-expected outcomes are encoded quantitatively via midbrain dopaminergic (DA) activity, it has been less addressed experimentally whether worse-than-expected outcomes are expressed quantitatively as well. We show that larger reward expectations upon unexpected reward omissions are associated with the preceding slower rise and following larger decrease (DA dip) in the DA concentration at the ventral striatum of mice. We set up a lever press task on a fixed ratio (FR) schedule requiring five lever presses as an effort for a food reward (FR5). The mice occasionally checked the food magazine without a reward before completing the task. The percentage of this premature magazine entry (PME) increased as the number of lever presses approached five, showing rising expectations with increasing proximity to task completion, and hence greater reward expectations. Fibre photometry of extracellular DA dynamics in the ventral striatum using a fluorescent protein (genetically encoded GPCR activation-based DA sensor: GRABDA2m ) revealed that the slow increase and fast decrease in DA levels around PMEs were correlated with the PME percentage, demonstrating a monotonic relationship between the DA dip amplitude and degree of expectations. Computational modelling of the lever press task implementing temporal difference errors and state transitions replicated the observed correlation between the PME frequency and DA dip amplitude in the FR5 task. Taken together, these findings indicate that the DA dip amplitude represents the degree of reward expectations monotonically, which may guide behavioural adjustment.

Conditioned approach behavior of SHR and SD rats during Pavlovian conditioning

Individual differences in reward-related learning are relevant to many behavioral disorders. Sensory cues that predict reward can become incentive stimuli that adaptively support behavior, or alternatively, cause maladaptive behaviors. The spontaneously hypertensive rat (SHR) expresses a genetically determined elevated sensitivity to delay of reward, and has been extensively studied as a behavioral model for attention deficit hyperactivity disorder (ADHD). We investigated reward-related learning in the SHR, comparing them to Sprague-Dawley (SD) rats as a reference strain. A standard Pavlovian conditioned approach task was used, in which a lever cue was followed by reward. Lever presses could occur while the lever was extended, but had no effect on reward delivery. The behavior of both the SHRs and the SD rats showed that they learnt that the lever cue predicted reward. However, the pattern of behavior differed between the strains. During lever cue presentation, SD rats pressed the lever more often and made fewer magazine entries than SHRs. When lever contacts that did not result in lever presses were analyzed, there was no significant difference between SHRs and SDs. These results suggest that the SHRs attributed less incentive value to the conditioned stimulus than the SD rats. During the presentation of the conditioned cue, cue directed responses are called sign tracking responses, whereas responses directed towards the food magazine are called goal tracking responses. Analysis of behavior using a standard Pavlovian conditioned approach index to quantify sign and goal tracking tendencies showed that both strains had a tendency towards goal tracking in this task. However, the SHRs showed a significantly greater goal tracking tendency than the SD rats. Taken together, these findings suggest that attribution of incentive value to reward predicting cues is attenuated in SHRs, which might explain their elevated sensitivity to delay of reward.

A history of low dose ethanol modulates ventral hippocampus activity during motivated behavior

More than half of the 130 million people in the U.S. who consumed alcohol within the last month did so at a level that did not meet diagnostic criteria for an alcohol binge. However, even these sub diagnostic drinking levels can have neurobehavioral outcomes. Clinical studies have shown that low levels of acute ethanol drinking soon after learning can enhance task consolidation and memory recall. Our preclinical data in C57BL6J mice show that a history of repeated, low dose ethanol (0.5g/kg) exposure increases sucrose reward motivation as measured by progressive ratio. The ventral hippocampus (vHPC) is increasingly considered a critical contributor to reward seeking and has been shown to be sensitive to chronic ethanol exposure at higher doses. The present study sought to determine whether daily, post‐training, low dose ethanol exposure can modulate vHPC activity during motivated behavior. To investigate this, we implanted mice with an electrode array to record vHPC neural activity during performance of a progressive ratio task. We also investigated vHPC activity around important behavioral events in the task, including lever pressing (when the animal is seeking the reward) and magazine entries (when the animal is checking for reward delivery). Our results demonstrate that saline control mice show suppression of vHPC activity following a lever press, while mice with a history of low dose ethanol exposure exhibit this suppression prior to a lever press. In contrast, both saline and ethanol‐exposed mice exhibit similar vHPC activity patterns surrounding magazine entry. These results suggest that a history of post‐training low dose ethanol exposure modulates vHPC activity during reward seeking. Further, this shift in vHPC suppression around a lever press may be associated with the enhanced motivation for sucrose observed in ethanol‐exposed mice. Future studies will use optogenetics to determine whether this shift in activity contributes to heightened reward motivation in ethanol exposed mice. A greater understanding of the neurobiological substrates impacted by ethanol exposure can help identify factors placing casual drinkers at risk for transition to alcohol use disorder.

Appetitive 50 kHz calls in a pavlovian conditioned approach task in Cacna1c haploinsufficient rats

We have previously shown that rats emit high-frequency 50 kHz ultrasonic vocalizations (USV) during sign- and goal-tracking in a common Pavlovian conditioned approach task. Such 50 kHz calls are probably related to positive affect and are associated with meso-limbic dopamine function. In humans, the CACNA1C gene, encoding for the α1C subunit of the L-type voltage-gated calcium channel CaV1.2, is implicated in several mental disorders, including mood disorders associated with altered dopamine signaling. In the present study, we investigated sign- and goal-tracking behavior and the emission of 50 kHz USV in Cacna1c haploinsufficent rats in a task where food pellet delivery is signaled by an appearance of an otherwise inoperable lever. Over the course of this Pavlovian training, these rats not only increased their approach to the reward site, but also their rates of pressing the inoperable lever. During subsequent extinction tests, where reward delivery was omitted, extinction patterns differed between reward site (i.e. magazine entries) and lever, since magazine entries quickly declined whereas behavior towards the lever transiently increased. Based on established criteria to define sign- or goal-tracking individuals, no CACNA1C rat met a sign-tracking criterion, since around 42% of rats tested where goal-trackers and the other 58% fell into an intermediate range. Regarding USV, we found that the CACNA1C rats emitted 50 kHz calls with a clear subject-dependent pattern; also, most of them were of a flat subtype and occurred mainly during initial habituation phases without cues or rewards. Compared, to previously published wildtype controls, Cacna1c haploinsufficent rats displayed reduced numbers of appetitive 50 kHz calls. Moreover, similar to wildtype littermate controls, 50 kHz call emission in Cacna1c haploinsufficent rats was intra-individually stable over training days and was negatively associated with goal-tracking. Together, these findings provide evidence in support of 50 kHz calls as trait marker. The finding that Cacna1c haploinsufficent rats show reductions of 50 kHz calls accompanied with more goal-tracking, is consistent with the assumption of altered dopamine signaling in these rats, a finding which supports their applicability in models of mental disorders.

Effects of Motivational Downshifts on Specific Pavlovian-Instrumental Transfer in Rats.

BackgroundPavlovian stimuli predictive of appetitive outcomes can exert a powerful influence on the selection and initiation of action, a phenomenon termed outcome-selective Pavlovian-instrumental transfer (sPIT). Rodent studies suggest that sPIT is insensitive to motivational downshift induced by outcome devaluation, an effect that is, however, relatively underexplored.MethodsHere we examined in detail the effects of distinct shifts in motivation from hunger to a state of relative satiety on sPIT in rats.ResultsA motivational downshift by outcome-specific devaluation immediately prior to testing markedly reduced overall lever responding and magazine entries but left intact the sPIT effect. A motivational downshift prior testing by (1) giving ad libitum rather than restricted access to maintenance diet in the home cage for 24 hours or by (2) a systemic blockade of hormone secretagogue receptor subtype 1A receptors to inhibit orexigenic actions of ghrelin both reduced overall lever responding and magazine entries. Moreover, these latter motivational downshifts reduced the sPIT effect; however, the sizes of the sPIT effects were still large.ConclusionsCollectively, our rodent findings indicate that major effects of various motivational downshifts are overall inhibition of lever pressing and magazine approach, possibly reflecting reduced general motivation. The observed effects of motivational downshifts on sPIT have implications with regard to the role of general motivating effects in sPIT and to the contribution of Pavlovian-instrumental interactions to excessive food seeking as well as obesity in humans.

Frustrative nonreward and cannabinoid receptors: Chronic (but not acute) WIN 55,212-2 treatment increased resistance to change in two reward downshift tasks

Assessing the role of cannabinoid (CB) receptors in behavior is relevant given the trend toward the legalization of medicinal and recreational marijuana. The present research aims at bridging a gap in our understanding of CB-receptor function in animal models of frustrative nonreward. These experiments were designed to (1) determine the effects of chronic administration of the nonselective CB1-receptor agonist WIN 55,212-2 (WIN) on reward downshift in rats and (2) determine whether the effects of chronic WIN were reducible to acute effects. In Experiment 1, chronic WIN (7 daily injections, 10 mg/kg, ip) accelerated the recovery of consummatory behavior after a 32-to-4% sucrose downshift relative to vehicle controls. In addition, chronic WIN eliminated the preference for an unshifted lever when the other lever was subject to a 12-to-2 pellet downshift in free-choice trials, but only in animals with previous experience with a sucrose downshift. In Experiment 2, acute WIN (1 mg/kg, ip) reduced consummatory behavior, but did not affect recovery from a 32-to-4% sucrose downshift. The antagonist SR 141716A (3 mg/kg, ip) also failed to interfere with recovery after the sucrose downshift. In Experiment 3, acute WIN administration (1 mg/kg, ip) did not affect free-choice behavior after a pellet downshift, although it reduced lever pressing and increased magazine entries relative to vehicle controls. The effects of chronic WIN on frustrative nonreward were not reducible to acute effects of the drug. Chronic WIN treatment in rats, like chronic marijuana use in humans, seems to increase resistance to the effects of frustrative nonreward.

Partial reinforcement in rat autoshaping with a long CS: Effects of pramipexole and chlordiazepoxide on sign and goal tracking

Abstract In Pavlovian autoshaping, sign-tracking responses (lever pressing) to a conditioned stimulus (CS) are usually invigorated under partial reinforcement (PR) compared to continuous reinforcement (CR). This effect, called the PR acquisition effect (PRAE), can be interpreted in terms of increased incentive hope or frustration-induced drive derived from PR training. Incentive hope and frustration have been related to dopaminergic and GABAergic activity, respectively. We examined the within-trial dynamics of sign and goal tracking in rats exposed to 20-s-long lever presentations during autoshaping acquisition under PR vs. CR conditions under the effects of drugs tapping on dopamine and GABA activity. There was no evidence of the PRAE in these results, both groups showing high, stable sign-tracking response rates. However, the pharmacological treatments affected behavior as revealed in within-trial changes. The dopamine D2 receptor agonist pramipexole (0.4 mg/kg) suppressed lever pressing and magazine entries relative to saline controls in a within-subject design, but only in PR animals. The allosteric benzodiazepine chlordiazepoxide (5 mg/kg) failed to affect either sign or goal tracking in either CR or PR animals. These results emphasize the roles of dopamine and GABA receptors in autoshaping performance, but remain inconclusive with respect to incentive hope and frustration theories. Some aspects of within-trial changes in sign and goal tracking are consistent with a mixture of reward timing and response competition.

On the role of responses in Pavlovian acquisition.

A defining feature of Pavlovian conditioning is that the unconditioned stimulus (US) is delivered whether or not the animal performs a conditioned response (CR). This has lead to the question: Does CR performance play any role in conditioning? Between the 1930s and 1970s, a consensus emerged that CR acquisition is driven by CS-US (CS, conditioned stimulus) experiences, and that CRs play a minimal role, if any. Here we revisit the question and present 2 new quantitative methods to evaluate whether CRs influence the course of learning. Our results suggest that CRs play an important role in Pavlovian acquisition, in such paradigms as rabbit eye blink conditioning, pigeon autoshaped key pecking, and rat autoshaped lever pressing and magazine entry. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Delay Gradients for Spout-Licking and Magazine-Entering Induced by a Periodic Food Schedule

The present experiments studied impulsivity by manipulating the delay between target responses and presentation of a reinforcer. Food-deprived SHR, WKY, and Wistar rats were exposed to a fixed-time 30-s schedule of food pellet presentation until they developed stable patterns of water spout-licking and magazine-entering. In successive phases of the study, a resetting delay contingency postponed food delivery if target responses (licks or entries) occurred within the last 1, 2, 5, 10, 20, 25, or 28 s of the inter-food interval. Response-food delays were applied independently for the two behaviors during separate experimental phases, and order of presentation and the behavior that was punished first were counterbalanced. Licking was induced in the order of Wistar > SHR > WKY, and magazine entries were in the order of SHR > WKY > Wistar. Magazine entries showed steeper delay gradients than licking in SHR and Wistar rats but were of similar great inclination in the WKY rats. The different responses were differentially sensitive to delays. This suggests a different ordering of them in the interval between reinforcers. It also has implications for attempts to change impulsive behavior, both in terms of the nature of the response and its removal from reinforcing consequences.

Discrimination Reversal Facilitates Contextual Conditioning in Rats’ Appetitive conditioning

Abstract Two experiments were conducted with the goal of exploring the effect of experiencing associative interference upon concurrent learning about conditioned stimuli and contexts in rats’ appetitive conditioning. During the first training phase, two groups of rats received a conditioned stimulus (CS1) followed by food, whereas another conditioned stimulus (CS2) was presented alone. During a second training phase, discrimination was reversed in group R, while it remained the same in group D. A new conditioned stimulus (CS3) was concurrently trained followed by food during this second Phase (Experiment 1). Reversal discrimination did not facilitate concurrent conditioning of the new stimulus, but there was a trend towards facilitation of contextual conditioning, measured by magazine entries in the absence of stimuli, that was confirmed in Experiment 2. These results suggest that the interference treatment may facilitate context conditioning under circumstances and with boundaries that are yet to be established.

Temporal distributions of schedule-induced licks, magazine entries, and lever presses on fixed- and variable-time schedules.

In this article, schedule-induced drinking (SID) refers to increased drinking by hungry rats exposed to intermittent delivery of food pellets. Two major accounts of SID differ in their explanation of why such drinking tends be concentrated soon after pellet delivery. Temporal discrimination theories propose that drinking is a form of displacement activity that occurs when a pellet is least likely. Adventitious reinforcement theories propose that drinking is displaced to early in an interpellet interval (IPI) by magazine-directed behavior that occurs toward the end of an IPI. The main aim of this study was to examine the latter response-competition account by recording distributions of both licking and magazine entries as SID developed when pellets were delivered to different groups either on a fixed-time (FT 30 s) or on a variable-time schedule (VT 30 s), as in Experiment 1. Although VT 30-s schedules produced essentially flat distributions of magazine entries, licking still tended to be concentrated early in an IPI. Furthermore, there was no indication (Experiments 1 and 2) that magazine entry distributions developed ahead of licking distributions. Experiment 3 examined distributions of lever presses instead of licks: Initially high rates of lever pressing declined both with response-independent schedules (FT and VT) and when a minimal response-dependency was introduced (recycling conjunctive schedule), yet this response also tended to be most frequent soon after pellet delivery. Overall, the data were generally consistent with temporal conditioning theories.

Responses compete and collaborate, shaping each others' distributions: Commentary on Boakes, Patterson, Kendig, and Harris (2015).

Boakes, Patterson, Kendig, and Harris (2015) showed that schedule-induced drinking (SID), typically concentrated in the first half of the interpellet interval, is not moved there exclusively by competition from magazine entries, and that not all arbitrary responses can be maintained by adventitious reinforcement. They attribute such inferences to Killeen and Pellón (2013) and Patterson and Boakes (2012), and on that basis reject their explanation for the excessive nature of many adjunctive responses as a result of reinforcement. It is a mistaken attribution, as Killeen and Pellón emphasized that reinforcers act on many competing interim and terminal responses. That attribution is a minor oversight on the authors' part; their return to a discredited motivational account is, however, a major blunder. It discards the seminal recent advances in understanding the nature of schedule-induced responses (e.g., those of Patterson and Boakes), and even the positive contributions of their own article: Their data show very strong correlations between magazine entries and drinking, providing much more evidence for response competition than their microanalysis provides against it.

Role of the striatopallidal pathway in renewal and reacquisition of alcohol seeking.

The ventral pallidum (VP) is a key component of the neural circuitry mediating relapse to drug seeking, but the critical afferent pathways to VP recruited during relapse remain poorly understood. We studied the role of the nucleus accumbens core (AcbC) → VP pathway in ABA renewal and reacquisition of alcohol seeking. Rats received application of adenoviral vectors encoding eYFP, ChR2(H134R), or eNpHr3.0 to AcbC and implantation of fiber optic cannulas into VP to permit photostimulation of AcbC terminals there. Rats were then trained to self-administer alcoholic beer in 1 context (A), extinguished in a second context (B), tested in the extinction (ABB) and training (ABA) contexts, and were then tested for reacquisition of alcoholic beer seeking. There was ABA renewal of alcohol seeking, but neither optogenetic excitation nor inhibition of the AcbC → VP pathway affected this renewal. In contrast, optogenetic inhibition of the AcbC → VP striatopallidal pathway reduced reacquisition of alcohol seeking-measured either by the number of active nosepokes emitted or by the number of alcohol rewards earned and consumed. Moreover, optogenetic excitation of the AcbC → VP striatopallidal pathway increased magazine entries during reacquisition test. This finding shows the importance of the AcbC → VP pathway in controlling relapse when the drug reinforcer is present on test and is consistent with a role for the AcbC → VP pathway in regulating the hedonic or incentive motivational properties of drug reinforcers.

Impaired cognition after stimulation of P2Y1 receptors in the rat medial prefrontal cortex.

We hypothesize that cortical ATP and ADP accumulating in the extracellular space, eg during prolonged network activity, contribute to a decline in cognitive performance in particular via stimulation of the G protein-coupled P2Y1 receptor (P2Y1R) subtype. Here, we report first evidence on P2Y1R-mediated control of cognitive functioning in rats using bilateral microinfusions of the selective agonist MRS2365 into medial prefrontal cortex (mPFC). MRS2365 attenuated prepulse inhibition of the acoustic startle reflex while having no impact on startle amplitude. Stimulation of P2Y1Rs deteriorated performance accuracy in the delayed non-matching to position task in a delay dependent manner and increased the rate of magazine entries consistent with both working memory disturbances and impaired impulse control. Further, MRS2365 significantly impaired performance in the reversal learning task. These effects might be related to MRS2365-evoked increase of dopamine observed by microdialysis to be short-lasting in mPFC and long-lasting in the nucleus accumbens. P2Y1Rs were identified on pyramidal cells and parvalbumin-positive interneurons, but not on tyrosine hydroxylase-positive fibers, which argues for an indirect activation of dopaminergic afferents in the cortex by MRS2365. Collectively, these results suggest that activation of P2Y1Rs in the mPFC impairs inhibitory control and behavioral flexibility mediated by increased mesocorticolimbic activity and local disinhibition.

Increased behavioral output but intact goal-directed and habitual responding for food reward following early-life social deprivation in rats

Early-life social adversity, such as child neglect and institutionalized rearing, is associated with later-life difficulties of inhibitory control that may reflect altered attribution of salience to external stimuli. Studies in rats demonstrate that early-life social deprivation results in enhanced responsiveness to reward stimuli and conditioned reward cues. This study examined whether these effects are related to fundamental changes in appetitive conditioning processes involving instrumental goal-directed and habitual responding for food reward. Rats were reared either by the mother (maternal rearing; MR) or in complete isolation from the mother and litter (artificial rearing; AR) and tested as adults in two appetitive conditioning tasks. AR and MR rats did not differ in the amount of goal-directed effort they exerted to obtain food reward on progressive ratio schedules of reinforcement. AR and MR rats also did not differ in the shift from goal-directed to habitual responding on a random interval schedule and they were equally sensitive to changes in reward value. The major difference between AR and MR rats was that AR rats exhibited more non-instrumental responses (empty food magazine entries, ineffective lever presses). Thus, early-life social deprivation of rats through AR affects the expression of unreinforced extraneous behaviors when motivational requirements are high, but does not affect conditioned goal-directed and habitual responding to reward. The findings have implications for understanding what aspects of responsiveness to external stimuli may be selectively affected in disorders of inhibition associated with early-life social adversity.

Magazine approach during a signal for food depends on Pavlovian, not instrumental, conditioning.

In the conditioned magazine approach paradigm, rats are exposed to a contingent relationship between a conditioned stimulus (CS) and the delivery of food (the unconditioned stimulus, US). As the rats learn the CS-US association, they make frequent anticipatory head entries into the food magazine (the conditioned response, CR) during the CS. Conventionally, this is considered to be a Pavlovian paradigm because food is contingent on the CS and not on the performance of CRs during the CS. However, because magazine entries during the CS are reliably followed by food, the increase in frequency of those responses may involve adventitious ("superstitious") instrumental conditioning. The existing evidence, from experiments using an omission schedule to eliminate the possibility of instrumental conditioning (B. J. Farwell & J. J. Ayres, 1979, Stimulus-reinforcer and response-reinforcer relations in the control of conditioned appetitive headpoking (goal tracking) in rats. Learning and Motivation, 10, 295-312; P. C. Holland, 1979, Differential effects of omission contingencies on various components of Pavlovian appetitive conditioned responding in rats. Journal of Experimental Psychology: Animal Behavior Processes, 5, 178-193), is ambiguous: rats acquire magazine CRs despite the omission schedule, demonstrating that the response does not depend on instrumental conditioning, but the response rate is greatly depressed compared with that of rats trained on a yoked schedule, consistent with a contribution from instrumental conditioning under normal (nonomission) schedules. Here we describe experiments in which rats were trained on feature-positive or feature-negative type discriminations between trials that were reinforced on an omission schedule versus trials reinforced on a yoked schedule. The experiments show that the difference in responding between omission and yoked schedules is due to suppression of responding under the omission schedule rather than an elevation of responding under the yoked schedule. We conclude that magazine responses during the CS are largely or entirely Pavlovian CRs.

Response rate and reinforcement rate in Pavlovian conditioning.

Four experiments used delay conditioning of magazine approach in rats to investigate the relationship between the rate of responding, R, to a conditioned stimulus (CS) and the rate, r, at which the CS is reinforced with the unconditioned stimulus (US). Rats were concurrently trained with four variable-duration CSs with different rs, either as a result of differences in the mean CS-US interval or in the proportion of CS presentations that ended with the US. In each case, R was systematically related to r, and the relationship was very accurately characterized by a hyperbolic function, R = Ar/(r +c). Accordingly, the reciprocal of these two variables-response interval, I (= 1/R), and CS-US interval, i (= 1/r) - were related by a simple affine (straight line) transformation, I = mi+b. This latter relationship shows that each increment in the time that the rats had to wait for food produced a linear increment in the time they waited between magazine entries. We discuss the close agreement between our findings and the Matching Law (Herrnstein, 1970) and consider their implications for both associative theories (e.g., Rescorla & Wagner, 1972) and nonassociative theories (Gallistel & Gibbon, 2000) of conditioning. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

Effects of antipsychotic drugs on MK-801-induced attentional and motivational deficits in rats

BackgroundAttentional deficits that accompany schizophrenia are not effectively treated by available antipsychotic medications. Disruption of NMDA receptor function is often used to model aspects of this disorder in rodents. We used the 5-choice serial reaction time task (5CSRTT) to characterize attentional deficits caused by acute administration or withdrawal from chronic administration of the NMDA receptor antagonist MK-801, and determine if they are ameliorated by haloperidol or clozapine. MethodsAcute studies involved tests in the presence of MK-801: rats were administered haloperidol (0.008–0.125mg/kg, SC) or clozapine (0.16–2.5mg/kg, SC) in combination with MK-801 (0.25mg/kg, IP) prior to daily test sessions. Chronic studies involved tests in the absence of MK-801: following daily tests, rats were administered MK-801 (0.5mg/kg, IP) and tested 24h later in the absence or presence of haloperidol or clozapine. ResultsAcute MK-801 disrupted performance: it decreased accuracy while increasing omissions, premature responses, and magazine entries. Haloperidol reduced disruptive effects associated with increased activation, whereas it exacerbated other deficits. Clozapine dose-dependently attenuated several of the MK-801-induced performance deficits. Withdrawal from chronic MK-801 progressively increased omissions and response latencies and decreased premature responding, suggesting an amotivational state. Neither haloperidol nor clozapine ameliorated these performance deficits. DiscussionAcute administration and withdrawal from chronic MK-801 administration produced distinct behavioral profiles in the 5CSRTT. Acute MK-801 impaired attention and impulse control whereas chronic MK-801 withdrawal caused signs consistent with amotivation. Haloperidol and clozapine were more effective at attenuating deficits caused by acute MK-801 administration.