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PubMed1998

Piracetam inhibits Pavlovian extinction and reversal learning in a spatial task for rats.

Young male rats, trained in a spatial three-choice test, showed improved task acquisition after chronic treatment with piracetam (250 mg kg(-1)). After reaching a learning criterion, one group of animals was observed during Pavlovian extinction of the task skill and another group was assigned to reversal learning. The rate of extinction was slowed down in piracetam treated specimens compared to control animals. During reversal training, a new choice had to be learned while the previously acquired choice was no longer reinforced. Acquisition of the new skill was significantly impeded by piracetam in contrast to acquisition of the first skill, which was facilitated. Also during reversal learning, the piracetam treated group persevered longer than the control group in repeating the first acquired choice at the expense of learning the new choice. It is therefore suggested, that the impediment of reversal learning was caused by inhibition of extinction. In an open-field test, the time spent exploring in motion was increased by piracetam while the velocity of locomotion was unaffected by the drug. In a novelty test, piracetam increased the rate of loss of interactions with the novel object.

Animals↗
PubMed1976

Origins of anthropoid intelligence. III. Role of prefrontal system in delayed-alternation and spatial-reversal learning in a prosimian (Galago senegalensis).

A species of prosimian (bush baby, Galago senegalensis) was tested on delayed-alternation and spatial-reversal learning before and after ablation of prefrontal cortex. The results show that normal performance on the two behavioral tasks depend on different subdivisions of the MD-prefrontal system. Delayed alternation is disrupted by prefrontal lesions which cause degeneration in the lateral division of MD while spatial-reversal learning is disrupted by lesions causing degeneration of the medial division of MD. Therefore, the bush baby prefrontal system can be subdivided either on behavioral or anatomical grounds into at least two chief parts. Because of several similarities in the MD-prefrontal system of bush baby and monkey despite their remote common ancestry, it can be concluded that the differentiation of the MD-prefrontal system into distinct divisions and the involvement of this system in delayed alternation and spatial reversal are features probably as old as the order Primates itself. It can be further concluded that the further evolution of the anthropoid variety of prefrontal system beyond this common primate stage probably depended on selective pressure on abilities other than those measured here.

Animals↗
PubMed1986

Lesions of the retrosplenial cortex produce deficits in reversal learning of the rabbit nictitating membrane response: implications for potential interactions between hippocampal and cerebellar brain systems.

The effect of bilateral lesions of the retrosplenial cortex on discrimination reversal learning of the rabbit nictitating membrane response was examined. Results showed that animals with such lesions were not impaired in their ability to acquire a cross-modality discrimination, but were severely impaired in their ability to reverse the discrimination once it was learned. All animals failed at the reversal phase of the task because they displayed high levels of conditioned responding to both the CS+ and the CS-. Thus bilateral damage to the retrosplenial cortex results in deficits in reversal learning that are highly similar to those observed after bilateral hippocampectomy. These findings are interpreted within a conceptual framework that characterizes multisynaptic projections from the hippocampus to the retrosplenial cortex, and ultimately to the cerebellum, as responsible for the behavioral expression of learning-related changes in hippocampal pyramidal cell activity.

Animals↗
PubMed2003

The atypical antipsychotic ziprasidone, but not haloperidol, improves phencyclidine-induced cognitive deficits in a reversal learning task in the rat.

The glutamate/N-methyl-D-aspartate receptor antagonist phencyclidine (PCP) has been shown to induce both positive and negative symptoms of schizophrenia, as well as cognitive deficits, thus providing a relatively valid model of psychosis. Isolation rearing from weaning in the rat has been proposed as a non-pharmacological model of psychosis. The aim of the present study was to explore the validity of a combination of these techniques to model cognitive dysfunction associated with schizophrenia. The present study evaluates the effects of the novel antipsychotic ziprasidone and the typical antipsychotic haloperidol in their ability to reverse the cognitive deficit induced by PCP in isolation reared rats and social controls. Rats housed in social isolation (n = 25) or in groups of five (n = 25) from weaning were food deprived and trained to respond for food in an operant reversal learning paradigm. PCP at 1.0 and 1.5 mg/kg (intraperitoneally, i.p.) significantly and selectively impaired reversal task performance in both groups of rats. This impairment was not significantly improved following the coadministration of haloperidol (0.05 mg/kg, i.p.). Higher haloperidol doses (0.1 and 0.25 mg/kg, i.p.) were found to impair task performance, with the social animals being more sensitive than isolation-reared animals. In contrast, ziprasidone (2.5 mg/kg, i.p.) reversed the impairment caused by PCP. This was significant in social animals, while in isolates there was a non-significant enhancement in performance of the reversal task with ziprasidone compared to PCP alone. Thus, PCP produced a selective reversal learning deficit in rats, which was ameliorated following treatment with ziprasidone but not haloperidol. Rearing conditions did not influence performance of the test or the deficit produced by PCP.

Animals↗
PubMed1989

Verbalization of appropriate and inappropriate cues in discrimination reversal learning by moderately mentally retarded children.

Effects of verbalization on discrimination reversal learning for moderately mentally retarded children were examined under three training conditions. Predicted results indicated that verbalization of both appropriate and inappropriate cues within relevant dimension significantly facilitated reversal shift performance, as compared to verbalization of only appropriate cues or non-verbalization. Results were interpreted to be due to the fact that verbalization of both appropriate and inappropriate cues actually served to utilize attentional or verbal mediators in terms of combining appropriate with inappropriate cues within relevant stimulus dimension.

Adolescent↗
PubMed1986

Hippocampal lesions disrupt classical conditioning of cross-modality reversal learning of the rabbit nictitating membrane response.

The role of the hippocampus and subiculum in classical conditioning of tone-light discrimination reversal learning of the rabbit nictitating membrane response was investigated using aspiration lesions of both limbic structures. Only two of seven animals with hippocampal-subicular damage successfully reached reversal criteria within 21 days of conditioning, although all hippocampectomized animals learned the initial discrimination at rates equivalent to those of two control groups. Thus, previously reported deficits in two-tone reversal learning seen after similar lesions are not due to increased within-modality generalization to the conditioned stimuli (CS) serving as the CS+ and CS-.

Animals↗
PubMed1998

Restricted lesions to ventral prefrontal subareas block reversal learning but not visual discrimination learning in rats.

Previous studies have shown that extensive damage to the medial prefrontal cortex (mPFC) of rats causes reversal learning deficits. The mPFC of rats, however, consists of several subareas that are different from each other in both cytoarchitecture and neural connectivity, suggesting a functional dissociation among the mPFC subareas. In the present study, selective lesions of the mPFC of rats were made with a specially designed microknife whose intracranial placement could be controlled stereotaxically. Restricted lesions were made to each of the 3 parts of the mPFC: the anterior cingulate area (AC) (including the medial precentral area, PrCm), the prelimbic area (PL), and the infralimbic area (IL). One week after surgery, rats were trained in an aversively motivated visual discrimination task in a novel rotating T-maze. After reaching the acquisition criterion, rats were trained in a reversal task in the same maze. No difference was found in acquisition between control and mPFC lesioned rats. However, lesions of either the PL or the IL produced a marked deficit in the reversal task. This behavioral deficit was not found in rats with lesions of the AC. The results indicate that the mPFC of rats is not essential for discrimination learning, but that each of the 2 ventral subareas of the mPFC, PL, and IL, plays a critical role in reversal learning.

Animals↗
PubMed1984

[Discrimination reversal learning in rats under the treatment of chlordiazepoxide: effect of overtraining].

A total of 48 rats were run in a black-white discrimination (original) learning task to the learning criterion of 18/20 correct responses. Correct responses were rewarded by food and a non-correction method was used. One group was intraperitoneally injected with 15 mg/kg of chlordiazepoxide (CDP) and the other with physiological saline (SAL), 30 min prior to the beginning of the daily trials. For half of the rats (NOT) of each group, reversal learning began on the next day after reaching the criterion, and for the other half (OT), 100 additional trials(overtraining) were given before the reversal. The results showed that CDP as well as overtraining significantly retarded the reversal learning. CDP had no effect on the original learning. Further analysis of the data revealed that perseverative errors early in the reversal increased significantly under the conditions of CDP and overtraining, but trials to criterion after the first occurrence of the correct response were not affected by both CDP and overtraining. These results were discussed in terms of CDP's disinhibitory action and overtraining reversal effect in such relatively easy discrimination task as in the present experiment.

Animals↗
PubMedDate not supplied

Arginine vasopressin facilitates reversal learning in albino, but not hooded rats.

Male Holtzman albino and Long-Evans hooded rats were administered one microgram of arginine vasopressin (AVP) or a placebo each day after the acquisition trials of a visual white-black discrimination. Animals were then trained in the reversal of the discrimination. Performance was assessed by the number of trials to criterion during acquisition and reversal. Treatment with AVP resulted in significantly fewer trials to criterion during reversal learning in Holtzman albino rats, but did not influence reversal learning in Long-Evans hooded rats. These results provide evidence that AVP may have differential actions on memory processes in different strains of rats.

Animals↗
PubMed2003

Orbital prefrontal cortex mediates reversal learning and not attentional set shifting in the rat.

It has been demonstrated previously that lesions to medial prefrontal cortex in rats impair the shifting of attentional set between perceptual features of complex stimuli [J. Neurosci. 20 (2000) 4320], a result that mirrors the deficit found in humans and monkeys [Nature 380 (1996) 69; Behav. Neurosci. 110 (1996) 872; J. Neurosci. 17 (1997) 9285; Neuropsychologia 29 (1991) 993]. These data imply functional homology between rat medial prefrontal cortex and primate prefrontal cortex.In marmoset monkeys, there is a double dissociation between the effects of lesions of lateral prefrontal cortex, which impair shifting of attentional set, and lesions of orbital prefrontal cortex, which result in impairments of reversal of stimulus-reward contingencies, leaving attentional set-shifting capacities intact [Nature 380 (1996) 69; Behav. Neurosci. 110 (1996) 872; J. Neurosci. 17 (1997) 9285]. The present investigation examined whether lesions to rat orbital prefrontal cortex would produce deficits in reversal learning in the absence of deficits in shifting attentional set, as seen in monkeys. Rats were trained to perform an attentional set-shifting task that is formally the same as that used in monkeys and humans. In a single session, rats performed a series of discriminations, including acquisitions and reversals. Damage to orbital prefrontal cortex in the rats did not disrupt the ability to acquire, maintain or shift attentional set. We report here the same selective impairment in reversal learning in rats as seen in primates with orbital prefrontal cortex lesions.

Analysis of Variance↗
PubMed2006

Reduced orbitofrontal-striatal activity on a reversal learning task in obsessive-compulsive disorder.

CONTEXT: The orbitofrontal cortex (OFC)-striatal circuit, which is important for motivational behavior, is assumed to be involved in the pathophysiology of obsessive-compulsive disorder (OCD) according to current neurobiological models of this disorder. However, the engagement of this neural loop in OCD has not been tested directly in a cognitive activation imaging paradigm so far. OBJECTIVE: To determine whether the OFC and the ventral striatum show abnormal neural activity in OCD during cognitive challenge. DESIGN: A reversal learning task was employed in 20 patients with OCD who were not receiving medication and 27 healthy controls during an event-related functional magnetic resonance imaging experiment using a scanning sequence sensitive to OFC signal. This design allowed investigation of the neural correlates of reward and punishment receipt as well as of "affective switching," ie, altering behavior on reversing reinforcement contingencies. RESULTS: Patients with OCD exhibited an impaired task end result reflected by a reduced number of correct responses relative to control subjects but showed adequate behavior on receipt of punishment and with regard to affective switching. On reward outcome, patients showed decreased responsiveness in right medial and lateral OFC as well as in the right caudate nucleus (border zone ventral striatum) when compared with controls. During affective switching, patients recruited the left posterior OFC, bilateral insular cortex, bilateral dorsolateral, and bilateral anterior prefrontal cortex to a lesser extent than control subjects. No areas were found for which patients exhibited increased activity relative to controls, and no differential activations were observed for punishment in a direct group comparison. CONCLUSIONS: These data show behavioral impairments accompanied by aberrant OFC-striatal and dorsal prefrontal activity in OCD on a reversal learning task that addresses this circuit's function. These findings not only confirm previous reports of dorsal prefrontal dysfunction in OCD but also provide evidence for the involvement of the OFC-striatal loop in the pathophysiology of OCD.

Adult↗
PubMed2006

Relationship between limbic and cortical 5-HT neurotransmission and acquisition and reversal learning in a go/no-go task in rats.

RATIONALE: Specific brain structures have been suggested to be involved in impulsive responding assessed by a variety of operant tasks. Central serotonin (5-HT) function has also been widely implicated in impulsivity; however, little research has addressed the regional aspect of 5-HT roles in different impulsive indices of task performance. OBJECTIVE: We analyzed the relationships between acquisition and reversal learning in a go/no-go task as different behavioral measures of impulsivity and focal concentrations of 5-HT and its metabolites in the brain. MATERIALS AND METHODS: Rats administered with parachloroamphetamine (PCA) and vehicle were tested in both acquisition and reversal phases in a go/no-go visual discrimination task. Neurochemical analysis was performed to determine 5-HT concentrations in micropunched brain tissues. RESULTS: PCA administration induced regionally 5-HT depletion in the brain and impaired learning performance in both tests. For both tests, significant negative correlations between learning performance and 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were observed in the medial prefrontal cortex (mPFC) and amygdala (Amyg). In contrast, significant negative correlations between learning performance and 5-HT and 5-HIAA concentrations were observed for the orbitofrontal cortex (OFC) exclusively in the reversal learning phase. CONCLUSIONS: The present data indicate that 5-HT neurotransmission to the mPFC and Amyg is involved in inhibitory control over responses to discriminated stimuli associated with the go/no-go paradigm common to both tests. In contrast, 5-HT neurotransmission to the OFC is especially involved in additional processes associated with reversal learning.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2006

The role of medial prefrontal cortex in context-specific inhibition during reversal learning of a visual discrimination.

Rats with medial prefrontal cortex or sham lesions were trained on a visual discrimination task designed for the eight-arm radial maze. After reaching asymptotic performance on this task, both groups were divided into sub-groups that would experience reversal learning in the same or different context from original training. The results showed that both groups reversed in the different context had accelerated learning compared to the groups reversed in the same context. Reversal learning in rats with medial prefrontal cortex damage was faster than sham animals in the same context. These and other results from a transfer test suggest that the medial prefrontal cortex participates in the behavioral effects of a context-specific inhibitory association acquired during visual discrimination learning.

Animals↗
PubMed1986

Influence of the varieties of differentiation training and prefrontal lesions on retention and reversal learning of avoidance responding in dogs.

The postoperative retention and reversal of go, no-go avoidance reflex differentiation with symmetrical and asymmetrical reinforcement were studied in dogs with prefrontal lesions and unoperated controls. The general pattern of the influence of such experimental variables as type of differentiation task an,d quality and arrangement of conditioned stimuli' was similar to that oberved preoperatively. However, prefrontal surgery changed the interactions between these experimental variables. The modifying role of the medial and the lateral parts of prefrontal cortex on the retention of differentiation and on reversal learning is discussed.

Acoustic Stimulation↗
PubMed1997

Effects of radiofrequency versus neurotoxic cingulate lesions on spatial reversal learning in mice.

Mice with radiofrequency (RF) lesions of the posterior (PC) or anterior (AC) cingulate cortex were trained on spatial discrimination reversal learning in a T-maze. The results were compared with those obtained in an earlier study after ibotenic acid (IBO) cingulate lesions. PC-RF lesions facilitated the initial discrimination and first reversal, whereas they retarded subsequent reversals; in contrast, PC-IBO lesions yielded a deficit on the initial discrimination and first reversal, but had no effect on subsequent reversals. AC-IBO, but not AC-RF lesions, precluded the formation of a learning set across reversals. These data suggest that cingulum transection, which accompanies RF but not IBO lesions, can mask or even antagonize the specific effects of cingulate damage. Consequently, inferences made from the effects of conventional lesions to assess and distinguish the functions of the two cingulate areas appear subject to caution.

Animals↗
PubMedDate not supplied

Effects of perinatal PCB exposure on discrimination-reversal learning in monkeys.

Monkeys exposed to PCB mixtures during gestation and lactation were tested on two-choice discrimination-reversal learning (DR). In Experiment 1, offspring of mothers fed 1.0 ppm Aroclor 1248, and offspring born 1.5 years after maternal exposure to 2.5 ppm Aroclor 1248 ended did not differ from controls on spatial, color or shape DR problems. In Experiment 2, offspring of mothers fed 0.25 or 1.0 ppm Aroclor 1016 and offspring born 3 years after maternal exposure to 2.5 ppm Aroclor 1248 ended were tested on the same spatial, color and shape problems, but a spatial problem with color and shape as irrelevant cues was inserted after the initial spatial problem. Performance of the high dose Aroclor 1016 offspring was impaired on the initial spatial problem, and facilitated on the shape problem. Performance of the Aroclor 1248 postexposure offspring was facilitated on the shape problem. This apparently facilitatory effect may represent a failure of PCB-exposed monkeys to learn the irrelevancy of the shape cue when it was initially presented.

Adipose Tissue↗
PubMed2002

Position reversal learning in aged Japanese macaques.

We examined aged and young monkeys using a multiple position reversal task to investigate declines in cognitive functions with aging. The task consisted of an original learning task (simple position discrimination task) and a reversal learning task. While the performance of the aged monkeys was not different from that of the young monkeys in the original learning task, the aged monkeys showed a poorer performance than the young monkeys in the reversal learning task. According to our response analysis, the poor performance of aged monkeys in the reversal learning was not caused mainly by repetition of error responses, but rather by the impairment of understanding of the association between stimulus and reward. These results suggest that the prefrontal cortex, particularly the medial orbital cortex, is impaired with aging.

Aging↗
PubMed1982

Effect of haloperidol and chlorpromazine on reversal learning of normal and striatectomized rats in a Y-maze.

Haloperidol (0.05-0.1 mg/kg) and chlorpromazine (0.5-1.0 mg/kg) improved reversal learning avoidance responses in a Y-maze, decreased intersessional fluctuations of errors and decreased the number of spontaneous exits from a correctly selected chamber. After bilateral lesions of the striatum this effect disappeared. Brain lesions also attenuated the ability of neuroleptics to suppress amphetamine-induced stereotypy and and accompanying defects in avoidance responses. The improvement of avoidance behavior by neuroleptics may be related to the reduction of spatial preference caused by functional asymmetry between the bilateral nigro-striatal systems.

Amphetamine↗