Terguride, a dopamine D(2) partial agonist, as a discriminative stimulus in rats

Drug discrimination training with terguride, a 9, 10-transdihydrogenated derivative of lisuride, was carried out using a two-lever food-reinforced procedure (FR 10) in rats, to investigate its influence on central dopaminergic (DA) and serotonergic (5-HT) functions. The terguride (0.05mg/kg, i.p.) discrimination was established within 64 +/- 5 training sessions (mean +/- S.E.) and was stably maintained thereafter. Higher doses of terguride could not be used for discriminative training due to response disruption. In generalization tests with terguride, drug-appropriate responding increased dose-dependently and reached levels of 45 and 99% at 0.01 and 0.05mg/kg i.p. The D(2) agonist lisuride at low doses and the DA autoreceptor agonist (-)-3-PPP substituted for terguride. The DA agonist apomorphine and the 5-HT agonist 5-MeO-DMT produced dose-dependent but incomplete substitution. The D(1) agonist SKF38393, the DA antagonist haloperidol, the D(2) antagonist sulpiride, the D(1) antagonist SCH23390, the 5-HT(1A) agonist 8-OH-DPAT, the 5-HT(1B) agonist m-CPP and the 5-HT(2) agonist DOI were not generalized. In antagonism tests, sulpride completely blocked the terguride-appropriate response, but SCH23390 and the 5-HT antagonist methysergide did not. These results indicate that discriminative stimulus properties of terguride in rats are mediated primarily by activation of receptors with characteristics similar to those of presynaptic D(2) autoreceptors.