Bar-press Response Research Articles

Symbolic Generalization of Discriminative Functions in Accordance with a Five-Member Comparative Relational Network

Three experiments investigated the symbolic generalization (transformation) of discriminative (bar-pressing) functions in accordance with a five-member arbitrary relational comparative network (A–B–C–D–E) in adults. Following nonarbitrary relational training and testing to establish the contextual functions of MORE-THAN and LESS-THAN for two abstract images, participants received arbitrary relational training and testing. One group received training on “More-than” baseline relations (e.g., B > A, C > B, D > C, and E > D) and another group received training on “Less-than” baseline relations (A A and A < C, etc.) and exposed to a bar-press training phase, which trained a low, steady rate bar-pressing response function to the middle stimulus (C) in the relational network. In Experiment 1, testing involved a quasi-random order of presentation of probe stimuli and half of the participants responded in accordance with the predicted relational network (i.e., pressed less to A and B and more to D and E, than to C). In Experiment 2, none of the participants showed the predicted performance when the probe stimuli were presented in a fixed order (A–B–C–D–E), whereas three out of four participants in Experiment 3 responded in accordance with the predicted relational network when the test was repeated. These findings indicate the importance of identifying methodological factors that may potentially influence the symbolic generalization of discriminative functions.

Comparison of the MK-801-induced increase in non-rewarded appetitive responding with dopamine agonists and locomotor activity in rats

Systemic administration of the noncompetitive N-methyl-D-aspartate (NMDA)- receptor antagonist, MK-801, has been proposed to model cognitive deficits similar to those seen in patients with schizophrenia. Evidence has shown that MK-801 increases the probability of operant responding during extinction, possibly modeling perseveration, as would be seen in patients with schizophrenia. This MK-801-induced behavioral perseveration is reversed by dopamine receptor antagonism. To further explore the role of dopamine in this behavioral change, the current study sought to determine if the MK-801-induced increase in non-rewarded operant responding could be mimicked by dopamine agonism and determine how it was related to locomotor activity. Male Long Evans rats were treated systemically with MK-801, cocaine, GBR12909 or apomorphine (APO) and given a single trial operant extinction session, followed by a separate assessment of locomotor activity. Both MK-801 (0.05 mg/kg) and cocaine (10 mg/kg) significantly increased responding during the extinction session and both increased horizontal locomotor activity. No dose of GBR-12909 (5, 10 or 20 mg/kg) was found to effect non-rewarded operant responding or locomotor activity. APO (0.05, 0.5, 2 or 5 mg/kg) treatment produced a dose-dependent decrease in both operant responding and locomotor activity. These results suggest the possibility that, rather than a primary influence of increased dopamine concentration on elevating bar-pressing responses during extinction, other neurotransmitter systems may be involved.

90 Intra-accumbens injection of a dopamine aptamer abates MK-801-induced cognitive dysfunction in a model of Schizophrenia

Aptamers are short, single-stranded sequences of DNA or RNA, which exhibit conformationally unique three-dimensional structures. Aptamer binding to target molecular substrates (from small molecules to proteins) demonstrates a high degree of affinity and specificity, in an analogous fashion to antigen–antibody binding. Aptamers offer several advantages over antibodies, including highly reproducible synthesis and ease of modification. Though the characteristics of aptamers and their applicability within the central nervous system show great potential, research in this area is limited. In the present work, the ability of a dopamine-binding DNA aptamer to regulate MK-801-induced cognitive deficits when injected into the nucleus accumbens was investigated. Systemic administration of the non-competitive NMDA-receptor antagonist, MK-801, has been proposed to model cognitive deficits similar to those seen in patients with schizophrenia. Rats were trained to bar press for chocolate pellet rewards then randomly assigned to receive an intra-accumbens injection of a DNA aptamer (200 nM; n = 7), tris buffer (n = 6) or a randomized DNA oligonucleotide (n = 7). Animals were then treated systemically with MK-801 (0.1 mg/kg) and tested for their ability to extinguish their bar-pressing response. Injection of 200 nM dose of the dopamine aptamer reversed this MK-801-induced elevation in lever pressing to levels as seen in rats not treated with MK-801. Tests for activity showed that the aptamer did not impair locomotor activity. Results demonstrate the in vivo utility of DNA aptamers as tools to investigate neurobiological processes in preclinical animal models of mental health disease.

Valence dependent asymmetric release of norepinephrine in the basolateral amygdala.

Emerging evidence from literature on humans suggests the valence of emotionally laden environmental stimuli may dictate whether amygdala activation is greater in one hemisphere relative to the contralateral side. However, only a paucity of animal studies attempt to unravel the mechanisms underlying the selective, valence-dependent initiation of activity in the amygdala of opposing hemispheres. The present studies assessed whether exposure to positive or negative appetitive conditions in an operant learning task differentially impacts norepinephrine activation of the left versus right amygdala, respectively. Dialysate samples of norepinephrine were collected from the basolateral nucleus of male Sprague-Dawley rats. Fluctuations in norepinephrine activity were sampled during training conditions involving an abrupt shift (i.e., increase or decrease) in the magnitude of food rewards normally provided for bar press responses. In a subsequent study, dialysate samples of norepinephrine were collected before, during, and after presentation of a negatively valenced stimulus involving footshock delivery during Pavlovian fear conditioning. Norepinephrine concentrations in the left but not right basolateral amygdala were elevated in groups presented with a positive experience of an unexpected increase in food reward after bar pressing (p < .01), relative to respective controls. In contrast, exposure to negatively valenced events involving a reduction in expected food rewards after bar pressing or presentation of a footshock during fear conditioning produced significant increases in norepinephrine output sampled from only the right but not left basolateral amygdala. These findings demonstrate that the valence of a learning event is selective in initiating asymmetric activation of the basolateral amygdala.

Differential involvement of endogenous opioids in sucrose consumption and food reinforcement

Endogenous opioids within the central nervous system are postulated to mediate hedonic aspects of feeding behavior. To identify the relevant endogenous opioid receptor ligands, mice lacking one or two of the opioid peptide families β-endorphin, enkephalins or dynorphins were tested for sucrose preference in a two-bottle free-choice drinking paradigm under drug-naïve conditions and following treatment with an opioid antagonist (1 mg/kg naloxone i.p.) or saline. Basal sucrose consumption was unaltered in all of the knockout genotypes compared to their congenic wild-type C57BL/6 littermates during 0.5 and 6 h access to a bottle containing 2, 4, 8, or 16% sucrose and a second bottle containing water. Moreover, all mutant genotypes and wildtype mice exhibited a similar compensatory decrease in overnight food intake following the extra caloric load from 6 h sucrose access. Although these basal responses to sucrose were unaffected by the knockout genotypes, naloxone reduced sucrose consumption by 50% compared to saline treatment during the first 0.5 h in wild-type and β-endorphin knockout mice, but had no effect in enkephalin knockouts, β-endorphin and enkephalin double knockouts, or dynorphin knockouts. These data suggest that naloxone reduces sucrose consumption in wild-type mice by blocking endogenous enkephalin and/or dynorphin signaling, but not β-endorphin. Dynorphin knockouts in the current study had bar-pressing responses for a palatable food reinforcer in an operant procedure under free-feeding conditions similar to wild-type mice while we found in a previous study that β-endorphin and enkephalin knockout mice had reduced motivation to respond [Hayward MD, Pintar JE, Low MJ. Selective reward deficit in mice lacking beta-endorphin and enkephalin. J Neurosci 2002;22:8251–8258.]. We conclude from these studies directly comparing three strains of opioid peptide knockout mice that enkephalin and dynorphin can modulate sucrose preference but are not necessary to support sucrose consumption. However, dynorphin was not necessary to support wildtype levels of operant responding suggesting that only enkephalin and β-endorphin modulate conditioned food reinforcement.

Positive and negative reinforcers: How about the second and third functions?

To begin, Skinner made the fundamentally important distinction of two types of conditioning, respondent and operant. Involving different research traditions, apparatus, and methods, it is also the case that the two are studied separately. That has had effects that have not been fully recognized and dealt with. Very centrally, it is important to realize and deal with the fact that both types of conditioning inevitably occur in research even though the experimenter is interested in studying only one. When food is presented as an unconditioned stimulus in classical conditioning, it perforce is contingent on some behavior whose strength will thereby be affected. When a food pellet is presented contingent on a key peck or bar press in operant conditioning, perforce that reinforcing stimulus will also elicit emotional responses (salivation being one) that will be conditioned to the experimental chamber. (This is true because food as a stimulus has both a reinforcing function and an emotion-eliciting function; see Staats, 1975.) As Michael astutely laid out 30 years ago and Baron and Galizio (2005) have affirmed, the effects on the operant behavior that is reinforced are the same for both positive and negative reinforcers. But that does not deal with the respondent conditioning involved. And it does not consider behaviors other than the one that is reinforced. With respect to the first, if all the conditioning occurring to the experimental animal were measured, the difference in positive and negative reinforcers would become evident. When withdrawal of a negative reinforcer is the contingency that increases the strength of the operant behavior, the animal also will be conditioned to a negative emotional response to the experimental chamber (for a negative reinforcer must be introduced before it can be withdrawn). However, when a positive reinforcer is used to strengthen the operant behavior, a positive emotional response will be conditioned to the stimulus of the operant chamber. Someone disinterested in emotional responding might say “Who cares? We are concerned with operant behavior.” So it is important to indicate that as a result of the emotional conditioning during operant conditioning, operant behavior other than the bar press will be affected. Let me sketch an experimental apparatus and procedure for studying what is involved. The experimental apparatus would be an operant conditioning chamber with a see-through wall opposite the bar manipulandum. The see-through wall would contain a door that when open would connect to another, empty chamber. The study would involve 2 rats. One would be conditioned to make a bar-press response using food, and the other would be so conditioned using escape from shock. Then each would be placed in the outer chamber, and the door would be opened to the operant chamber so that each had access to the operant chamber. The animal whose bar press had been reinforced with food would enter the chamber, go to the bar, and sniff around it and the feeder. The shock-escape animal would not enter the chamber. A child who is punished unless he behaves well in school may learn as well as a child who behaves the same because of positive reinforcement. But the two will learn different emotional responses to school, and that will affect their behavior towards school, under open conditions. These principles—including the last effect that involves the third function of stimuli, discriminative control—are described more fully in Harms and Staats (1978), Staats (1975, 1996), Staats and Hammond (1972), and Staats and Warren (1974). Behaviorally, when all behavior is taken into account, there is a great difference between positive and negative reinforcers. Basic studies should be conducted with animals to systematically treat the relation of respondent and operant conditioning over the various behavioral variables (e.g., deprivation–satiation). (The above apparatus is only a first suggestion.) Beginning studies with humans are available (Harms and Staats 1978; Staats & Hammond, 1972; Staats & Warren, 1974), other studies have been interpreted in terms of the principles, and behavior analyses have been made of functional human behavior (see Staats, 1975, 1996). There is a very large field of animal and human research here for our field to pursue.

Differential involvement of the central amygdala in appetitive versus aversive learning

Understanding the function of the distinct amygdaloid nuclei in learning comprises a major challenge. In the two studies described herein, we used c-Fos immunolabeling to compare the engagement of various nuclei of the amygdala in appetitive and aversive instrumental training procedures. In the first experiment, rats that had already acquired a bar-pressing response to a partial food reinforcement were further trained to learn that an acoustic stimulus signaled either continuous food reinforcement (appetitive training) or a footshock (aversive training). The first training session of the presentation of the acoustic stimulus resulted in significant increases of c-Fos immunolabeling throughout the amygdala; however, the pattern of activation of the nuclei of the amygdala differed according to the valence of motivation. The medial part of the central amygdala (CE) responded, surprisingly, to the appetitive conditioning selectively. The second experiment was designed to extend the aversive versus appetitive conditioning to mice, trained either for place preference or place avoidance in an automated learning system (INTELLICAGE). Again, much more intense c-Fos expression was observed in the medial part of the CE after the appetitive training as compared to the aversive training. These data, obtained in two species and by means of novel experimental approaches balancing appetitive versus aversive conditioning, support the hypothesis that the central nucleus of the amygdala is particularly involved in appetitively motivated learning processes.

The effect of electric shock on food carrying behavior in rats

We observed the foraging behavior of rats in the straight corridor. The corridor was 1600mm long, one end was patch and the opposite end was nest. Three subjects were trained bar-pressing response under FI-2 sec schedule at patch. The food items weighed 0.1, 0.2, 0.3, 0.4, and 0.5g, and one of them was randomly delivered as a reinforcer. In the first stage, animals' tendency to carry food to the nest increased as the size of those items increased (Figure 1). In the second stage, electric shocks were presented at patch under VT-10 min schedule in addition to the procedure of the first stage. Presentation of shocks enhanced food carrying compared with the first stage (Figure 1). The results indicate the validity of central place foraging model in rodents on which the forager adopt an optimal trade-off between item profitability and exposure predation.

Taste quality and intensity: Lessons from the Morrison technique

The nontoxic and nonshock Morrison operant technique was used to evaluate taste quality in rat and marmoset: response to a tastant test solution in pursuit of a pellet reward was dependent on making a choice between two bars that had been linked in discrimination training to qualitatively different stimulus pairs (NaCl versus either HCl, QHCl, or NH 4Cl). The percentage distribution of bar-press responses to test stimuli showed: (1) stability of quality across 0.069–0.3 M NaCl, 0.003–0.1 M HCl, and 0.0001–0.003 M QHCl; (2) for LiCl, a quality change consistent with human reports of a “sour” to “salty” shift; (3) a suggestion that the “salty-like” quality of NH 4Cl and NaCl are not perceptually equivalent; (4) NaNO 3 shares NaCl-like, QHCl-like, and NH 4Cl-like components; (5) CaCl 2, KCl, and MgCl 2 share QHCl-like and NH 4Cl-like components; and (6) responses to HCl and QHCl were not hedonically driven in the rat. Comparison of rank order correlations of single-unit firing rates to the distribution of bar-press responses for the same test stimulus concentration revealed that (7) no single level of the gustatory pathway exclusively accounts for the operant response distribution pattern to either simple or complex tastants, and (8) discriminations between tastants, one of which may be qualitatively complex, are not necessarily mediated only at levels proximal to the solitary nucleus. Thus, the Morrison discrimination technique effectively yields statements about gustatory quality without use of negative reinforcers and largely uninfluenced by tastant hedonics.

Functional Specificity of Ventral Striatal Compartments in Appetitive Behaviors

The nucleus accumbens and its associated circuitry subserve behaviors linked to natural or biological rewards, such as feeding, drinking, sex, exploration, and appetitive learning. We have investigated the functional role of neurotransmitter and intracellular transduction mechanisms in behaviors subserved by the core and shell subsystems within the accumbens. Local infusion of the selective NMDA antagonist, AP-5, into the accumbens core, but not the shell, completely blocked acquisition of a bar-press response for food in hungry rats. This effect was apparent only when infused during the early stages of learning. We have also recently shown that infusion of certain protein kinase inhibitors into the core also impairs learning in the same paradigm. These results suggest that plasticity-related mechanisms within the accumbens core, involving glutamate-linked intracellular second messengers, are important for response-reinforcement learning. In contrast to the core, which primarily connects to somatic motor output systems, the shell is more intimately linked to viscero-endocrine effector systems. We have shown that both AMPA and GABA receptors within the medial shell (but not the core) are critically involved in controlling the brain's feeding pathways, via activation of the lateral hypothalamus (LH). This effect is blocked by local inhibition of the LH in double-cannulae experiments and also strongly and selectively activates Fos expression in the LH. These results provide a newly emerging picture of the differentiated functions of this forebrain region and suggest an integrated role in the elaboration of adaptive motor actions.

Learning and memory in the FMR1 knockout mouse.

The fragile X [fra(X)] syndrome is manifested phenotypically as a developmental disability comprised mainly of moderate-to-severe mental retardation (MR). Deficits are especially evident in auditory and visual short-term memory. Recently, an FMR1 knockout mouse developed by the Dutch-Belgian Fragile X Consortium demonstrated significantly lower visual-spatial abilities than littermate controls. We wondered if these results were associated with learning per se or to performance deficits only. Thus, we examined learning and memory in male FMR1 knockout mice crossbred from Fvb and E129 strains, and in male Fvb control mice, using operant conditioning techniques. In Experiment 1, we demonstrated that two aged male FMR1 knockouts could acquire the necessary bar-press response to discriminate visual (L+) and auditory (N+) stimuli. In Experiment 2, we showed that three naive male knockouts and two naive male controls, all 12 weeks old, also learned to discriminate L+ and N+. A third component, a complex discrimination task, during which light and noise were presented concurrently without reinforcement (LN-) was added to each session. All knockouts acquired both L+ and N+ discriminative responses in fewer sessions and with higher discrimination ratios than either control. Moreover, all knockouts exhibited the typical response pattern associated with complex discrimination (LN-) tasks. However, neither control made the complex discrimination. Our findings were unexpected and raise issues concerning FMR1 mouse strains and their cognitive-behavioral testing.

Mother rats bar-press for pups: effects of lesions of the mpoa and limbic sites on maternal behavior and operant responding for pup-reinforcement

This series of studies explored the operant response rates for pup-reinforcement of female Sprague–Dawley rats that were either postpartum or cycling and sustained lesions of the medial preoptic area (mpoa), the lateral amygdala, the nucleus accumbens, or sham lesions. The last experiment tested the effects on operant responding of preventing direct access to pups in mpoa and sham-lesioned postpartum mothers. All animals were trained prior to mating on an FR-1 bar-press schedule to criterion (50 presses in 30 min) for a food (Froot Loops) reward in an operant chamber. At the end of pregnancy animals that were to be tested postpartum were provided in their home cages with six newborn foster pups; mother-litter interactions were observed on the last 3 days of pregnancy and throughout the postpartum period. On each of these same days after a period of separation from pups, females were tested in the operant box for delivery of rat pups. With each bar-press response, a rat pup rather than a Fruit Loop was delivered down a gentle shoot into the hopper. Non-postpartum, but maternal, multiparous animals who were showing estrous cycles were tested using the same procedures. The first and second studies showed that animals (both postpartum and as cycling multiparous animals) with mpoa lesions exhibited a significant reduction in bar-press rate for pup reinforcement in the operant box. In postpartum animals, amygdala lesions also produced a bar-press deficit, whereas nucleus accumbens lesions did not. All lesioned groups showed deficits in maternal responding in the home cage and deficits in retrieval in the operant box. These results indicate that systems associated with the mpoa mediate both the stereotypical maternal behaviors and pup-reinforcement. In contrast, the expression of home cage maternal behavior is dependent on the integrity of both the amygdala and nucleus accumbens, whereas operant responding need not be. These results indicate a dissociation of mechanisms mediating expression of the species-typical maternal behavior and pup-reinforcement.

Effect of experimental setting on learning and performance of Auditory Delayed Matching-to-Sample task in dogs.

Twelve dogs were trained in a new task for auditory recognition memory: auditory Delayed Matching-to-Sample (DMS). The animals were tested in two experimental settings using approach (Setting 1) or bar-press (Setting 2) responses. At the early stages of training, the learning took more trials in Setting 2, which was caused by different instrumental response and/or different relationship among manipulanda, stimuli, and reward in these two settings. The performance of the final task did not differ between settings and showed a gradual decline with extended delays. No differences were found in responding patterns or in dynamics of learning. Therefore, we conclude that the auditory DMS, trained in either setting, offers a valuable and reliable tool for studies of neural substrate of auditory recognition memory. The detailed analyses of the dogs' behaviour will allow to evaluate the subtle effects of experimental manipulations in future experiments, and for many reasons the data obtained from these two settings may be combined in further analyses.

Preferential localization of self-stimulation sites in striosomes/patches in the rat striatum.

Histological sections of the mammalian striatum reveal a "matrix" that is histochemically distinguishable from patches, or "striosomes". The latter are cross sections of a compartment that consists primarily of tube-shaped structures radiating through the matrix. As a test of the hypothesis that the function of the striosome/patch compartment includes the mediation of behaviors related to reward, the present study examined electrical self-stimulation of the caudoputamen in rats with electrodes in either of the two compartments. Rats acquired and maintained bar-pressing responses that were contingent on stimulation through electrodes making contact with striosomes/patches more reliably than animals with electrodes terminating exclusively in the matrix. The results provide in vivo evidence that the striosome/patch compartment is functionally differentiated from the matrix compartment: Stimulation centered in or around the striosome/patch compartment but not in the matrix led to rapid acquisition of a new behavior.

The method of training dogs in auditory recognition memory tasks with trial-unique stimuli.

Three adults dogs were trained in a auditory recognition delayed-matching-to-sample (DMS) task. The experimental setting consisted of one central speaker located in front of the dogs head, two side speakers with nearby response pedals and one rotary food delivery system. Three hundred twenty natural sounds were used as trial-unique stimuli. Sample stimuli were always given through the central speaker. After the delay of 1.5 s, both sample and testing stimuli were activated alternately through the two side speakers. Bar-press response toward the sample stimulus was rewarded by food. The DMS training was continued until attaining a criterion 90% correct responses in 90 consecutive trials. After a control pause, the dogs were retrained to the criterion, and then they were given performance tasks with delays extended to 10-, 30-, 60- and finally to 90-s, in blocks of 90 trials. Dogs required about 1,000 trials of auditory recognition memory training in order to reach the criterion. Their behavior was also stable after the control pause. The dogs performance declined gradually with extended delays reaching an average of 63.4% for the delay of 90 s. Results indicate that the DMS task with auditory stimuli alternating during the testing stage of trial, is a promising method for testing auditory recognition memory.

Sex-linked behavioural differences in mice expressing a human insulin transgene in the medial habenula

We previously reported that a human insulin transgene was specifically expressed in the medial habenula of the adult mouse brain, and that this expression was ascribed to the Δ-168 transgene. The present study analyses the possible behavioural consequences of this insulin transgene expression using measures of food intake, spontaneous activity, emotional reactivity, learning and extinction performance of an operant task. The Δ-168 transgenic mice did not differ from the C57BL/6 control mice as concerns food intake, behaviour in the open field, or emotional response in an elevated plus maze. On the other hand, measures of locomotor activity in a circular corridor revealed a significantly faster decline of spontaneous locomotor activity in male as compared to female Δ-168 transgenic mice. Moreover, as compared to female transgenic mice, male transgenic mice exhibited a deficit in the rate of acquisition and an acceleration of the rate of extinction of a bar press response in a Skinner box. In contrast, the behaviour of female transgenic mice did not differ from either male or female C57BL/6 control mice. The results of the present study demonstrate that the behavioural modifications observed in Δ-168 transgenic mice are sex-linked and suggest that these behavioural differences result from changes in the interaction (interface) between motivational and motor mechanisms mediated via the striato-habenulo-mesencephalic system.

Dependence of the proactive behavioral effects of theta-driving septal stimulation on stimulation frequency and behavioral experience: 1. Leverpress experiments

We tested whether hippocampal theta has frequency-specific functions related to anxiety. Male rats received chronic implants of septal and subicular electrodes to elicit and record theta. Two to six weeks later, experimental rats received thirty 3-sec trains of theta-driving septal stimulation daily for 10 days; controls were connected to the apparatus, but not stimulated. The results were as follows: 7.7-Hz or 8.3-Hz theta driving before acquisition of a fixed-ratio 5 (FR5) barpress response increased its resistance to extinction subsequently (Experiment 1). In contrast, 7.5-Hz theta driving before acquisition of the FR5 response facilitated its later extinction (Experiment 2). Finally, 8.3-Hz theta driving after acquisition of the FR5 response also facilitated its extinction (Experiment 3). Thus, theta-driving stimulation (1) has nonassociative behavioral effects, which (2) are exquisitely frequency specific (Experiments 1–2) and (3) are modified by associative processes during acquisition of an appetitive response (Experiment 3). Theta is involved in producing anxiety, but not via spatial, motor, or memorial mechanisms.

Age-related impairment in instrumental conditioning is restricted to initial acquisition.

Performance on a variety of cognitive tasks has been reported to decline across the life span. The present research evaluated appetitive instrumental learning in young and mature rats. In Experiment 1, subjects were trained to criterion, placed on extinction training to criterion, and subsequently retrained for a total of three cycles. Results indicated that mature animals were impaired in the initial acquisition of the bar-press response but reacquired the response as quickly as young animals. Resistance to extinction was not significantly impaired in the mature group, both groups increased resistance by the third extinction period, despite the brevity of reinforcement. In Experiment 2, young and mature subjects underwent appetitive instrumental training that continued beyond the acquisition criterion for the first experiment. After the response had been established (to criterion), performance levels were equivalent for young and mature subjects. The number of responses were not significantly different between young and mature groups on the day criterion was met; comparison of number of responses for 4 days after criterion also indicated no significant differences over days of training or between age groups. Examination of the number of responses occurring early in training indicated no significant group difference; hence, the earlier acquisition by young animals in Experiment 1 does not appear to reflect greater activity level in younger animals resulting in earlier and greater exposure to reinforced responses. Results may reflect the contribution of use-induced plasticity, such as long-term potentiation, within brain systems involved in learning and memory. These findings are consistent with evidence of the effects of use and disuse on neurobiological and cognitive function.

Prior and concurrent learning increases object exploration in the rat (Rattus norvegicus)

Two experiments were earned out to examine object-direct exploratory behaviour in the rat during and following learning. In Experiment 1, a group of rats were initially trained to press a bar to obtain food rewards. The animals were then observed in an open field containing various objects, but their bar-pressing responses were not rewarded. This form of extinction induced exploratory behaviour, particularly at the onset of the trials, and while the bar was present in the open field. Removal of the bar produced a lesser effect Experiment 2 examined object-directed behaviour during operant conditioning and extinction, and compared exploration directed towards familiar and novel objects. Results indicated mat exploration was enhanced during conditioning and at the onset of extinction, but by the end of the trials novel objects were preferred by both trained and untrained animals. The different amounts of object exploration produced during and after learning are discussed in terms of their possible adaptive benefits to the rat.

Linopirdine (DUP 996; AVIVA): Its effects in the morris water escape task and on retention of an incompletely acquired bar-press response in rodents

The present study assessed the effects of linopirdine, a putative cognition-enhancing drug, on the acquisition and retention of a bar-press response [continous reinforcement schedule (CRF)] in young Wistar rats. It was also investigated whether this substance influenced the acquisition and retention of a standard Morris water escape task by young NMRI mice and by young and old Wistar rats. Linopirdine was given subcutaneously (0.03, 0.1, 0.3, 1.0, or 3.0 mg/kg body wt.), 30 min before the first trial of a session and in one experiment immediately after the last trial of each session. A probe trial was given after the last acquisition session. In the CRF task, linopirdine did not affect the response latency and the 24-h retention of young rats. None of the parameters investigated in the Morris maze, including the escape latency (the time the animals need to find the platform), was affected by linopirdine in the rat and mouse experiments. This was also true for performance in the probe trial: linopirdine treatment did not affect the bias of the animals for the quadrant in which the platform had been positioned during acquisition. Thus, we found no experimental evidence for the hypothesized action of linopirdine as a cognition enhancer.