RT Journal Article
SR Electronic
T1 Discriminative stimulus properties of lergotrile.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 47
OP 52
VO 230
IS 1
A1 K A Cunningham
A1 P M Callahan
A1 J B Appel
YR 1984
UL http://jpet.aspetjournals.org/content/230/1/47.abstract
AB Although withdrawn from clinical trials because of liver toxicity, the ergot derivative lergotrile has been useful in the treatment of disorders involving dopaminergic systems (e.g., parkinsonism). In various biochemical and behavioral assays, this compound acts most potently as a dopamine (DA) agonist but also has DA antagonist as well as serotonin (5-HT) agonist properties. To elucidate further its effects in vivo, rats were trained to discriminate 0.5 mg/kg of lergotrile from saline in a two-lever water-reinforced task. In tests for similarities to other ergolines, dose-related substitutions were observed with lisuride (0.003-0.04 mg/kg) and d-lysergic acid diethylamide (0.01-0.08 mg/kg); partial substitution occurred with ergonovine (0.063-0.5 mg/kg). The DA agonist apomorphine (0.016-0.5 mg/kg) also substituted for lergotrile whereas the 5-HT agonist quipazine (0.25-2.0 mg/kg) elicited primarily saline-appropriate responding. Tests involving drug combinations indicated that the DA antagonist haloperidol (0.016-0.5 mg/kg) attenuated responding on the drug-appropriate lever; however, neither the DA (D2) antagonist sulpiride (2.0-16.0 mg/kg) nor the 5-HT antagonist BC-105 (1.0-4.0 mg/kg) had an effect upon the lergotrile cue. These results indicate that DA neuronal systems are probably more important than 5-HT neuronal systems in mediating the discriminative stimulus properties of lergotrile; however, the contribution of other neurotransmitter systems (e.g., norepinephrine) to these effects still must be evaluated.