The continuity of dopamine receptor antagonism can dictate the long-term behavioural consequences of a mesolimbic infusion of dopamine

Abstract

An infusion of dopamine for 13 days into the nucleus accumbens of rat caused biphasic peaks of hyperactivity responding during infusion and an enhanced locomotor responsiveness to the dopamine agonist (-)N-n-propylnorapomorphine [(-)NPA] after the infusion when rats where initially preselected as low activity responders to (-)NPA. Antagonism of the response to dopamine during the infusion by sulpiride, given every 8 hr (three daily doses provided 30 mg/kg, i.p., daily), could both facilitate spontaneous locomotor activity after the infusion, and potentiate the consequence of enhanced hyperactivity responding to (-)NPA, for at least 11 weeks. In contrast, when sulpiride was administered in a daily dose of 30 mg/kg but by continuous intraperitoneal infusion, not only were the events during the infusion prevented, without subsequent change in spontaneous locomotion after the infusion, but also the long-term consequences for responding to (-)NPA were prevented and the rats remained at their preselected low activity response levels. The repeated treatment with (-)NPA or the repeated/continuous treatment with sulpiride alone were not responsible for the changes observed. It is concluded that the consequence of intervention with sulpiride during a period of infusion of dopamine into the mesolimbic region depends on the degree and/or continuity of antagonism of dopamine receptors such that fluctuating antagonism (daily injections) can exacerbate, whilst a continuous and constant receptor antagonism (effected by infusion), can prevent the long-term consequences of increased sensitivity to challenge with a dopamine agonist.