Discriminative stimulus properties of lergotrile

Kathryn Cunningham, P. M. Callahan, J. B. Appel

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Although withdrawn from clinical trials because of liver toxicity, the ergot derivative lergotrile has been useful in the treatment of disorders involving dopaminergic systems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 eludidate 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 that 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.

Original languageEnglish (US)
Pages (from-to)47-52
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume230
Issue number1
StatePublished - 1984
Externally publishedYes

Fingerprint

Serotonin Receptor Agonists
Dopamine Antagonists
Dopamine Agonists
Serotonin
Pizotyline
Ergolines
Lisuride
Quipazine
Ergonovine
Lysergic Acid Diethylamide
Sulpiride
Serotonin Antagonists
Apomorphine
Parkinsonian Disorders
Haloperidol
Drug Combinations
Cues
Neurotransmitter Agents
Dopamine
Norepinephrine

ASJC Scopus subject areas

  • Pharmacology

Cite this

Discriminative stimulus properties of lergotrile. / Cunningham, Kathryn; Callahan, P. M.; Appel, J. B.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 230, No. 1, 1984, p. 47-52.

Research output: Contribution to journalArticle

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