The dopamine D2 partial agonist and antagonist terguride decreases heroin self-administration on fixed- and progressive-ratio schedules

Dopamine partial agonists have been suggested to be potential therapeutic candidates for pharmacological intervention in drug addiction. These drugs bind to dopamine receptors with high affinity and low intrinsic activity and are hypothesized to behave as functional antagonists in conditions of high dopaminergic tone. The aim of the present study was to characterize the effects of terguride, a partial dopamine agonist at the dopamine D-2 receptor, on intravenous heroin self-administration on fixed- and progressive-ratio schedules of reinforcement. The effects of terguride on oral sweet solution (4% sucrose) self-administration on a fixed-ratio schedule were also tested. Terguride dose-dependently decreased heroin self-administration on the fixed-ratio schedule and decreased the maximum number of responses for heroin self-administration on a progressive-ratio schedule. In contrast, terguride did not significantly affect oral sucrose self-administration. These data suggest that terguride may represent a novel pharmacological strategy for the treatment of opiate addiction. (C) 2010 Elsevier Inc. All rights reserved.