Calcium dependence of sensitised dopamine release in rat nucleus accumbens following amphetamine challengeimplications for the disruption of latent inhibition
作者:
E. Warburton,
S. Mitchell,
M. Joseph,
期刊:
Behavioural Pharmacology
(OVID Available online 1996)
卷期:
Volume 7,
issue 2
页码: 119-129
ISSN:0955-8810
年代: 1996
出版商: OVID
关键词: Amphetamine sensitisation;Calcium dependence;Dopamine;In vivodialysis;Latent inhibition;Locomotor activity;Nucleus accumbens;Ondansetron;Rat
数据来源: OVID
摘要:
Repeated amphetamine treatment results in sensitisation both of its behavioural effects, and of its dopamine (DA)-releasing effects on which the former largely depend. Understanding the nature of the sensitised response may help to explain behaviours which emerge only with repeated treatment, such as particular stereotypies and effects on social behaviour in animals, and links between these effects and the emergence of dependence and psychotic symptoms in humans. We show here that a single pretreatment with amphetamine (1 mg/kg) is sufficient to sensitise the locomotor response to amphetamine challenge (1 mg/kg) 24 h later. We have usedin vivomicrodialysis in the nucleus accumbens in unrestrained rats to demonstrate a corresponding potentiation in the DA response; the marked increase in accumbens dialysate DA following amphetamine (to 427% of basal) was significantly potentiated (to 675% of basal) by the pretreatmeat, without any alteration in the basal DA. There was also no change in the expected reduction in DA metabolites. Replacement of perfusate calcium by magnesium left the response to acute amphetamine challenge substantially unaffected, as expected from previous reports; however, the potentiation of the DA response by amphetamine pretreatment was prevented. Similarly the potentiated response was attenuated by administration of ondansetron, a 5HT-3 antagonist, (0.01 mg/kg) before each amphetamine treatment. The ability of amphetamine to disrupt latent inhibition (LI), which Is also disrupted in acute schizophrenia, has been suggested to provide a model of schizophrenia linking underlying cognitive deficits with the DA theory of the disorder. Since LI is disrupted by two systemic administrations of amphetamine 24 h apart, but not by one, the present results are consistent with the concept that It is the calcium, and hence impulse, dependence of increased accumbal DA release, rather than its magnitude, which is critical for the disruption of LI.
点击下载:
PDF
(937KB)
返 回