Ergot Alkaloids As Dopamine Agonists: Comparison in Two Rodent Models
European Journal of Pharmacology, 37 (1976) 295-302 295 © North-Holland Publishing Company, Amsterdam - Printed in The Netherlands ERGOT ALKALOIDS AS DOPAMINE AGONISTS: COMPARISON IN TWO RODENT MODELS GILL ANLEZARK, CHRIS PYCOCK and BRIAN MELDRUM Department of Neurology, Institute of Psychiatry, Denmark Hill, London, SE5 8AF, U.K. Received 18 December 1975, revised MS received 20 February 1976, accepted 26 February 1976 G. ANLEZARK, C. PYCOCK and B. MELDRUM, Ergot alkaloids as dopamine agonists: comparison in two rodent models, European J. Pharmacol. 37 (1976) 295-302. A series of ergot alkaloids, together with the DA agonists apomorphine and piribedil, were tested for protec- tive effects against audiogenic seizures in an inbred strain of mice (DBA/2) and for induction of circling behaviour in mice with unilateral destruction of one nigrostriatal DA pathway. The order of potency against audiogenic sei- zures was apomorphine> ergocornine> bromocryptine > ergometrine> LSD> methysergide > piribedil while that observed in the rotating mouse model was apomorphine> ergometrine> ergocornine> brornocryptine > piribedil. LSD caused only weak circling behaviour even when administered in high doses (> 1 mg/kg). Methyser- gide was ineffective. Prior administration of the neuroleptic agent haloperidol blocked the effect of DA agonists and of ergot alkaloids in both animal models. The possible action of ergot alkaloids as DA agonists is discussed. Ergot alkaloids Audiogenic seizures Dopamine agonists Circling behaviour 1. Introduction gic synapses, in two rodent pharmacological models. The first model studied is 'audiogen- The pharmacology of the ergot alkaloids is ic' seizures in genetically susceptible mice. complex and not well understood. Peripheral- The severity of the seizure responses to audi- ly, they act on smooth muscle as 5-hydroxy- tory stimulation can be modified by a variety tryptamine (5-HT) antagonists (Goodman and of drugs believed to act on monoaminergic Gilman, 1971) and as a-adrenergic blockers transmission in the brain (Lehmann, 1970).
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