Long-term consequences of antagonism by neuroleptics of behavioural events occurring during mesolimbic dopamine infusion.

Rats selected as low-activity responders to peripherally administered (-)N-n-propylnorapomorphine [(-)NPA] were subjected to a 13-day continuous infusion of dopamine bilaterally into the nucleus accumbens (0.48 microliter/hr, 25 micrograms in 24 hr). This caused biphasic increases in spontaneous levels of hyperactivity with peaks occurring between days 2-5 and 8-12 of infusion. Two weeks after the infusion was withdrawn the low-activity status of the animals, to (-)NPA challenge, converted to high-activity and remained at this changed level for 18 to 20 weeks. The effects of sulpiride (2.5 mg/kg, i.p. daily) or haloperidol (0.025 mg/kg, i.p. daily) on the behavioural changes during infusion and after its withdrawal were assessed by administration on days 1-4 to inhibit the first peak of the enhanced spontaneous locomotion, on days 8-11 to inhibit the second peak, on days 1-4 and 8-11 to inhibit both peaks, on days 6-9 to influence the "trough" of behavioural responding between the peaks of hyperactivity, and on days 1-11 to modify all components of hyperactivity responding to infusion of dopamine. The usual consequence of infusion, the conversion of low-activity to high-activity responders to (-)NPA, was not prevented by any treatment with neuroleptic. It is concluded that the long-term consequences (up to 1 year) of a brief period (13 days) of overactivity induced by mesolimbic infusion of dopamine cannot be prevented by daily treatment with haloperidol or sulpiride in doses adequate to prevent the behavioural expression of the effects of the dopamine stimulation during its infusion.