The role of dopamine and serotonin in the discriminative stimulus effects of lisuride

FJ White and JB Appel

The discriminative stimulus properties of the clinically important ergot derivative lisuride hydrogen maleate (LHM) were investigated by training groups of rats (13 per group) to discriminate either of three training doses of LHM (0.02, 0.08 or 0.32 mg/kg) from saline. Dose- response tests showed that the three LHM cues were specific to the dose used during training and the dose-response curve became more steep as the training dose increased. In substitution tests, the direct dopamine (DA) agonists apomorphine and lergotrile substituted for LHM and the potency order of the LHM-like effect (LHM greater than apomorphine greater than lergotrile) corresponded to previous electrophysiological and biochemical results. The indirect DA agonist d-amphetamine did not substitute for LHM. The direct serotonin (5-HT) agonists quipazine, MK- 212 and 5-methoxy-N,N-dimethyltryptamine produced dose-dependent, but incomplete, substitution for LHM which covaried with LHM training dose. In antagonism tests, only drug capable of blocking DA receptors, haloperidol and methiothepin, attenuated the LHM cues; the 5-HT antagonists cyproheptadine, BC-105 and xylamidine were ineffective. These data indicate that the primary neuronal action mediating the discriminative stimulus effects of a wide range of LHM doses was direct activation of central DA receptors. The 5-HT agonist actions of LHM proved to be secondary in that 5-HT agonists substituted only partially for LHM and 5-HT antagonists failed to attenuate LHM cues.

Volume 221, Issue 2, pp. 421-427, 05/01/1982
Copyright © 1982 by American Society for Pharmacology and Experimental Therapeutics