The effects of d-amphetamine, alpha-flupenthixol, and mesolimbic dopamine depletion on a test of attentional switching in the rat

A test of attentional switching was devised for the rat in which it obtained sucrose reinforcement by an appropriate nose-poke response that discriminated which of two visual events terminated first, in a specially designed chamber. The effect of mesolimbic dopamine depletion (to 20% of control values) produced by infusions of 6-hydroxy-dopamine (6-OHDA) into the nucleus accumbens (N. Acc) on stable discrimination was measured alone and in the presence of a range of doses of d-amphetamine (0.4–2.3 mg/kg IP). The 6-OHDA lesion of the N. Acc impaired post-operative performance transiently by reducing choice accuracy and slowing response latency. By post-operative days 12–16, however, performance recovered to control levels and was not differentially affected by a mainpulation of task difficulty. d-Amphetamine produced dose-dependent performance impairments, which were antagonised by the 6-OHDA treatment. In a second group of N. Acc lesioned rats, the neuroleptic alpha-flupenthixol (0.1–1.0 mg/kg) led to fewer trials being completed and longer latencies than in the sham-operated control group. The results are discussed in terms of the possible attentional mechanisms underlying the d-amphetamine-induced disruption of performance mediated by the N. Acc and of the implications for psychopathology resulting from possible dysfunction of this region.