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Alterations in dopamine and 5-hydroxytryptamine (5-HT) function during barbiturate dependence and withdrawal in mice

Department of Pharmacology, University of Bristol Medical School, University Walk, Bristol BS8 1TD, UK

D. Dawbarn

Department of Pharmacology, University of Bristol Medical School, University Walk, Bristol BS8 1TD, UK

P.V. Taberner

Department of Pharmacology, University of Bristol Medical School, University Walk, Bristol BS8 1TD, UK

Mice were rendered barbiturate-dependent by chronic feeding with barbital-con taining food. Brain dopamine turnover was significantly increased in barbital withdrawal, whereas 5-hydroxytryptamine (5-HT) turnover was significantly decreased. Severity of with drawal was assessed by measuring the convulsions following a dose of 33 mg/kg mer captopropionate (MPA). The neurotoxins 6-hydroxydopamine and 5,6-dihydroxytryptamine as well as metergoline (5 mg/kg) increased the severity of MPA convulsions. Quipazine (20 mg/ kg) attenuated the convulsions. The results are consistent with the hypothesis that diminished 5-HT function may contribute to the barbital withdrawal syndrome. Behavioural responses to serotonergic drugs were enhanced in barbital-dependent mice compared to controls, but [³H]- 5-HT binding to crude membrane fractions was similar in both groups with a single high affinity site.

Journal of Psychopharmacology, Vol. 1, No. 2, 101-108 (1987)
DOI: 10.1177/026988118700100207


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