Behavioural rigidity and rule-learning deficits following isolation-rearing in the rat: neurochemical correlates

Jones, G. H.; Marsden, C.A.; Robbins, Trevor W.

doi:10.1016/s0166-4328(05)80050-6

Cited by 166 publications

(108 citation statements)

References 58 publications

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“…Animals are required to inhibit a previously rewarded strategy and acquire the new strategy. Thus, effective performance requires animals to demonstrate flexibility, attention and motivation, to suppress a previously learned response and implement a new response (Jones et al, 1991). Failure to switch, or perseveration on the previously learned response, can be readily observed in patients with schizophrenia undertaking tasks such as the Wisconsin Card Sorting test (Pantelis et al, 1999;Liddle, 2000).…”

Section: Reversal Learningmentioning

confidence: 99%

Animal models of cognitive dysfunction and negative symptoms of schizophrenia: Focus on NMDA receptor antagonism

Neill

Barnes

Cook

et al. 2010

Pharmacology & Therapeutics

478

322

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Cognitive deficits in schizophrenia remain an unmet clinical need. Improved understanding of the neuro-and psychopathology of these deficits depends on the availability of carefully validated animal models which will assist the development of novel therapies. There is much evidence that at least some of the pathology and symptomatology (particularly cognitive and negative symptoms) of schizophrenia results from a dysfunction of the glutamatergic system which may be modelled in animals through the use of NMDA receptor antagonists. The current review examines the validity of this model in rodents. We review the ability of acute and sub-chronic treatment with three non-competitive NMDA antagonists; phencyclidine (PCP), ketamine and MK801 (dizocilpine) to produce cognitive disturbances of relevance to schizophrenia in rodents and their subsequent reversal by first-and second-generation antipsychotic drugs. Effects of NMDA receptor antagonists on the performance of rodents in behavioural tests assessing the various domains of cognition and negative symptoms are examined: novel object recognition for visual memory, reversal learning and attentional set shifting for problem solving and reasoning, 5-choice serial reaction time for attention and speed of processing; in addition to effects on social behaviour and neuropathology. The evidence strongly supports the use of NMDA receptor antagonists to model cognitive deficit and negative symptoms of schizophrenia as well as certain pathological disturbances seen in the illness. This will facilitate the evaluation of much-needed novel therapies for improved therapy of cognitive deficits and negative symptoms in schizophrenia.

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Section: Reversal Learningmentioning

confidence: 99%

Animal models of cognitive dysfunction and negative symptoms of schizophrenia: Focus on NMDA receptor antagonism

Neill

Barnes

Cook

et al. 2010

Pharmacology & Therapeutics

478

322

View full text Add to dashboard Cite

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“…We measured this tendency by examining the ability of each subject to suppress a previously learnt response in a spatial extinction task (c.f. [31]). …”

Section: Maze Tasksmentioning

confidence: 99%

“…Since they stem from decreased behavioural inhibition, stereotypies caused by clinical or experimentally-induced basal ganglia dysfunction form part of a suite of changes in behaviour. These include enhanced rates of behavioural initiation [20,40]; 'impulsivity' [59]; impaired performance in tasks where responses must be suppressed or slowed [20,40,59]; the inappropriate repetition, or 'perseveration' of previous actions [20,39], which impairs performance in tasks such as extinction learning [23,31,48,67]; and a concurrent knowledge-action dissociation in such tasks, whereby human subjects know (and report) the correct response to make but are unable to suppress automatic repetition of a previous, incorrect response [67]. Thus along with stereotypies, isolationreared primates show poor abilities to suppress inap-propriate behaviour in extinction [7,27], while the stereotypy frequencies of human subjects with autism and schizophrenia correlate with their inappropriate repetition of responses in gambling or sequence-generation tasks [23,67].…”

Section: Introductionmentioning

confidence: 99%

Evidence for a relationship between cage stereotypies and behavioural disinhibition in laboratory rodents

Garner

Mason

2002

Behavioural Brain Research

218

163

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Cage stereotypies */abnormal, repetitive, unvarying and apparently functionless behaviours */are common in many captive animals, sometimes resulting in self-injury or decreased reproductive success. However, a general mechanistic or neurophysiological understanding of cage stereotypies has proved elusive. In contrast, stereotypies in human mental disorder, or those induced by drugs or brain lesions, are well understood, and are thought to result from the disinhibition of behavioural selection by the basal ganglia. In this study, we found that the cage stereotypies of captive bank voles also correlate with signs of altered response selection by the basal ganglia. Stereotypic bar-mouthing in the caged voles correlated with inappropriate responding in extinction learning, impairments of response timing, evidence of a knowledge-action dissociation, increased rates of behavioural activation, and hyperactivity. Furthermore, all these signs intercorrelated, implicating a single underlying deficit consistent with striatal disinhibition of response selection. Bar-mouthing thus appears fundamentally similar to the stereotypies of autists, schizophrenics, and subjects treated with amphetamine or basal ganglial lesions. These results represent the first evidence for a neural substrate of cage stereotypy. They also suggest that stereotypic animals may experience novel forms of psychological distress, and that stereotypy might well represent a potential confound in many behavioural experiments. #

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“…The second, 'indirect pathway' inhibits competing plans and movements, thus mediating the smooth transition between elements (Norman & Shallice 1986;Albin et al 1989;Alexander et al 1990;Rolls 1994). Suppression of the indirect pathway, which results in a general state of behavioural disinhibition, seems to occur in all stereotypies for which a neurological basis is known (Luria 1965;Joyce & Iversen 1984;Sandson & Albert 1984;Norman & Shallice 1986;Albin et al 1989;Jones et al 1991;Hauber 1998). Do such changes in the control of behaviour similarly underlie the cage stereotypies of captive animals?…”

mentioning

confidence: 99%

Stereotypic route-tracing in experimentally caged songbirds correlates with general behavioural disinhibition

2003

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Repetitive, unvarying and apparently functionless behaviours called stereotypies are common in caged animals, but the mechanisms of cage stereotypy have remained elusive. We found that stereotypies correlate with a sign of altered brain functioning, the general disinhibition of behaviour, found in stereotyping human patients and animals treated with psychostimulants. We investigated route-tracing stereotypy in blue tits, Parus caeruleus, and marsh tits, P. palustris, caged in a behavioural research laboratory. In experiment 1, stereotypy correlated with disinhibition of responses, shown as persistent responding in extinction learning. In experiment 2a, stereotypy in blue tits correlated with repetitive sequence generation on a 'gambling task' that specifically measures disinhibited striatal functioning in humans and correlates with stereotypy in autistic and schizophrenic patients. In experiment 2b, the behavioural disinhibition correlated with stereotypy also affected food-storing behaviour in marsh tits, in particular their response to cache pilfering. In experiment 3, the sequencing of nonstereotypic home cage behaviour was correlated with stereotypy. Finally, changes in stereotypy induced by environmental enrichment correlated with changes in these measures of altered behavioural control. These results suggest that housing conditions that cause stereotypy thus alter many aspects of the behavioural control of caged subjects, mediated by altered striatal functioning. The implications for understanding cage stereotypies in laboratory, farm and zoo animals, and for laboratory-based behavioural experiments, are discussed. We suggest that improving housing conditions so that cage stereotypies do not develop would enhance the validity of laboratory-based behavioural research.

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Behavioural rigidity and rule-learning deficits following isolation-rearing in the rat: neurochemical correlates

Cited by 166 publications

References 58 publications

Animal models of cognitive dysfunction and negative symptoms of schizophrenia: Focus on NMDA receptor antagonism

Animal models of cognitive dysfunction and negative symptoms of schizophrenia: Focus on NMDA receptor antagonism

Evidence for a relationship between cage stereotypies and behavioural disinhibition in laboratory rodents

Stereotypic route-tracing in experimentally caged songbirds correlates with general behavioural disinhibition

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