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

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 [(3)H]- 5-HT binding to crude membrane fractions was similar in both groups with a single high affinity site.