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Modulation of dexamphetamine-induced compulsive gnawing—Including the possible involvement of presynaptic alpha-adrenoreceptors

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Abstract

In an investigation into the mechanism of amphetamine-induced compulsive gnawing in the mouse, the effects of a range of drugs were determined on the ED50 value for dexamphetamine. Injection of noradrenaline or methoxamine into the cerebral ventricles (i.c.v.), or peripheral injection of clonidine, caused marked potentiation. The alpha-adrenoreceptor blocking agents phentolamine piperoxane and yohimbine elevated ED50 values while phenoxybenzamine was without significant effect. Inspection of effects on individual doses of dexamphetamine showed that both phenoxybenzamine and phentolamine could potentiate the effectiveness of low doses of dexamphetamine. Beta-adrenoreceptor blockade, usingdl-propranolol or MJ1999, significantly enhanced compulsive gnawing;d-propranolol was inactive. The selective dopamine-blocking agent pimozide abolished compulsive gnawing, as did α-methyl-p-tyrosine. FLA63 also reduced compulsive gnawing. Cholinergic stimulation by carbachol and physostigmine i.c.v. or by arecoline antagonised dexamphetamine, while the muscarinic blocking agents atropine and hyoscine potentiated it. The 5-hydroxytryptamine (5-HT) depleting agent p-chlorophenylalanine potentiated the effect of low doses of dexamphetamine but had no net effect on ED50 values; reserpine behaved similarly. 5-HT itself abolished dexamphetamine gnawing. Clonidine caused marked potentiation of the gnawing induced by apomorphine. The results are discussed in terms of the possible involvement of several transmitter systems in modulating the compulsive gnawing syndrome.

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  1. Pharmacological laboratories, Department of Pharmacy, Aston University, B4 7ET, Birmingham, UK

    Karin V. Thomas & Sheila L. Handley

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  1. Karin V. Thomas
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  2. Sheila L. Handley
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Thomas, K.V., Handley, S.L. Modulation of dexamphetamine-induced compulsive gnawing—Including the possible involvement of presynaptic alpha-adrenoreceptors. Psychopharmacology 56, 61–67 (1978). https://doi.org/10.1007/BF00571410

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