The role of dopamine and serotonin in the discriminative stimulus effects of lisuride
White, F.J.; Appel, J.B.
Journal of Pharmacology and Experimental Therapeutics 221(2): 421-427
1982
ISSN/ISBN: 0022-3565 PMID: 7077537 Document Number: 196273
The discriminative stimulus properties of the clinically important ergot derivative lisuride hydrogen maleate (LHM) were investigated by training groups of rats (13/group) to discriminate either of 3 training doses of LHM (0.02, 0.08 or 0.32 mg/kg) from saline. Dose-response tests showed that the 3 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 > apomorphine > 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 [6-chloro-2-(1-piperazinyl)-pyrazine]hydrochloride] and 5-methoxy-N,N-dimethyltryptamine produced dose-dependent but incomplete substitution for LHM which covaried with LHM training dose. In antagonism tests, only drugs capable of blocking DA receptors, haloperidol and methiothepin, attenuated the LHM cues. The 5-HT antagonists cyproheptadine, BC-105 [4-[(1-methyl-piperidylidene-4)]9,10-dihydro-4H-benzo[4,5]cyclohepta[1,2b]thiophene] and xylamidine were ineffective. The primary neuronal action mediating the discriminative stimulus effects of a wide range of LHM doses was evidently direct activation of central DA receptors. The 5-HT agonist actions of LHM were secondary in that 5-HT agonists substituted only partially for LHM and 5-HT antagonists did not attenuate LHM cues.