Specific abnormalities in serotonin release in the prefrontal cortex of isolation-reared rats measured during behavioural performance of a task assessing visuospatial attention and impulsivity.

摘要

RATIONALE. Rats reared in social isolation exhibit hyperactivity and specific attentional disturbances in later adult life. These behavioural abnormalities may be relevant to impulsivity and other neuropsychiatric syndromes such as attention-deficit hyperactivity disorder and schizophrenia where disturbances in circuitry involving the prefrontal cortex have been identified. OBJECTIVE. To establish whether isolation-reared rats show a differential susceptibility to cognitive processes that depend on the prefrontal cortex and its monoaminergic innervation. METHODS. Rats were reared in isolation from postnatal day 28 or in social groups of four and trained on the five-choice serial reaction time task, which assesses spatially divided visual attention. Following a range of manipulations designed to tax visual attention and response control, in vivo microdialysis was used in conjunction with behavioural testing to assess dopamine (DA) and serotonin (5-HT) release in the prefrontal cortex, either under baseline conditions prior to task initiation, or during task performance. Subjects were challenged with amphetamine (0.125 mg/kg intravenously) every 15 min, commencing 15 min after the start of the task. RESULTS. Apart from being consistently slower to collect food rewards and showing more perseverative responses to an auditory distractor, isolates were unimpaired on accuracy, impulsivity and correct latency measures on the five-choice task. Basal levels of DA and 5-HT in the prefrontal cortex were also unaffected by isolation rearing. Amphetamine increased the speed of responding in control and isolation-reared animals and increased premature (impulsive) responding, but only in socially-reared animals. Cortical DA release increased to a similar extent in both groups following amphetamine challenge. By contrast, 5-HT release was attenuated in isolates under these conditions. CONCLUSIONS. These findings highlight a rather specific deficit in 5-HT release in the prefrontal cortex of isolation-reared rats, although this appears not to affect visual attentional function. Rather, these data may be relevant to reduced impulsiveness of isolation-reared rats on the five-choice task. These findings are important in the context of animal models of attentional disturbances in schizophrenia.