CENTRAL 5-HT DEPLETION ENHANCES IMPULSIVE RESPONDING WITHOUT AFFECTING THE ACCURACY OF ATTENTIONAL PERFORMANCE - INTERACTIONS WITH DOPAMINERGIC MECHANISMS

A series of ten experiments examined the effects of profound central 5 -HT depletion on attentional performance in the rat in the five-choice serial reaction time task, and also determined the effects of such de pletion on responding affected by d-amphetamine and by selective dopam ine receptor antagonists. Rats were trained to detect and locate brief visual stimuli randomly presented in one of five spatial locations. W hen performance had stabilised (> 80% correct, < 20% omissions), selec tive central 5-HT depletion was induced by intracerebroventricular adm inistration of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) follow ing pretreatment with both a noradrenergic and a dopaminergic re-uptak e inhibitor. The lesioned animals performed the five-choice serial rea ction time task with the same degree of accuracy as the sham-operated controls. However, 5-HT depletion reduced the percentage of omitted tr ials and increased the number of premature/anticipatory responses. Thi s pattern of behaviour following 5-HT depletion could not be attribute d to enhanced primary motivation as demonstrated by measures of food i ntake and latencies to collect food reinforcement. The lesion attenuat ed the increase of premature responding induced by high doses of syste mically administered d-amphetamine. 5-HT depletion also attenuated the dose-dependent decrease in accuracy induced by (-)-sulpiride, a D-2 r eceptor antagonist, although the effects of this drug on response late ncies and premature responding were similar in both groups. However, t he systemic administration of the D-1 receptor antagonist, SCH 23390, blocked the impulsive responding produced by the lesion as indicated b y a lack of lesion effects on the percentage of omitted trials and pre mature responding. The results suggest that central 5-HT depletion res ults in impulsive, fast responding, which nevertheless does not impair accuracy of visual discrimination performance. The increased impulsiv ity may be mediated by altered 5-HT-dopamine interactions, with the le sion removing an inhibitory influence over dopamine neurotransmission.