Effects of Drugs Affecting Endogenous Amines or Cyclic Nucleotides on Ethanol Withdrawal Head Twitches in Mice

Abstract

1 Twenty-four hours after ethanol withdrawal, dependent mice exhibited frequent head twitching. Naive mice exhibited similar twitching 15 min after treatment with 5-hydroxytryptophan (5-HTP) or 6 h after a-methyl-p-tyrosine (AMPT). Ethanol lessened the incidence of head twitches induced by any of these treatments. 5-HTP and AMPT each increased the incidence of head twitches induced by withdrawal of ethanol from dependent mice. 2 Drugs that affect the amount or activity of endogenous amines or cyclic nucleotides modified the incidence of head twitches. Nearly all drugs acted in the same direction on twitching elicited by any of these three treatments.3 The incidence was lessened by: (a) methysergide, methergoline, MA 1420, p-chlorophenylalanine and p-chloroamphetamine; (b) dopamine, noradrenaline, L-DOPA, amphetamine and apomorphine; (c) hyoscine and nicotine; and (d) adenosine triphosphate, dibutyryl cyclic adenosine-3',5'-monophosphate (db cyclic AMP) and prostaglandins El and E2.4 The incidence was increased by: (a) acetylcholine, carbachol and physostigmine; and (b) guanosine triphosphate, dibutyryl cyclic guanosine monophosphate (db cyclic GMP), theophylline and 3-isobutyl-l-methyl-xanthine. 5 These findings suggest that head twitching induced by these three treatments arises from a common biochemical mechanism, which may ultimately be a change in favour of cyclic GMP of the balance between this nucleotide and cyclic AMP within appropriate neurones. This imbalance appears to be elicited or increased by 5-hydroxytryptamine and acetylcholine and to be decreased by dopamine, noradrenaline and E prostaglandins. 6 Neither actinomycin D nor cycloheximide, given during the induction of ethanol dependence, altered the incidence of head twitches after ethanol withdrawal.

Head-Twitches Induced by p-Hydroxyamphetamine in Mice

“…Head-twitches have been regarded as an experimental model for hallucination, since many drugs that produce hallucination such as LSD (1-3) or mescaline (3) have induced head-twitches in mice, but 49-tetrahydrocannabinol did not (3). Fur thermore, similar head-twitches have been elicited by other treatments including admin istration of atropine (3), 5-hydroxytryp tophan (4-6), 5-hyroxytryptamine (5-HT) (7-10), and quipazine (11,12) and ethanol withdrawal (13,14). Thus, a major metabolite of amphetamine, p-OHA may be concerned with amphetamine-induced schizophrenia.…”

EFFECT OF APOMORPHINE AND ITS N‐PROPYL HOMOLOGUE ON ETHANOL WITHDRAWAL HEAD TWITCHES IN MICE

“…Methods Male Swiss-Webster mice, weighing 18 to 22 g at the start of treatment, came from Taconic Farms, N.Y., U.S.A. The treatment was that of Collier et al (1976) in which mice were dosed with 40% ethanol orally for 4 days (4 rising to 7 g/kg) and tested 24 h after ethanol withdrawal.…”

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Collier, Hammond & Schneider (1976) reported that apomorphine, given orally, decreased the incidence of head twitches induced by ethanol withdrawal. These results 'were confirmed in the present study.

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“…Introduction Collier, Hammond & Schneider (1976) found that mice twitch their heads after ethanol withdrawal and that various drugs, including L-DOPA and apomorphine, inhibit this twitching. They suggested that some of the active drugs may be useful in the clinical management of alcoholism.…”

“…The treatment was that of Collier et al (1976) in which mice were dosed with 40% ethanol orally for 4 days (4 rising to 7 g/kg) and tested 24 h after ethanol withdrawal.…”