REPEATED EXPOSURE OF RATS TO THE CONVULSANT AGENT FLUROTHYL ENHANCES 5‐HYDROXYTRYPTAMINE‐ AND DOPAMINE‐MEDIATED BEHAVIOURAL RESPONSES

Abstract

1 Rats were convulsed once daily for 7 days by exposure to the inhalant convulsant agent, flurothyl (Indoklon, bis (2,2,2-trifluouroethyl)ether). Twenty four hours after the final convulsion the rats were injected with tranylcypromine (20 mg/kg) followed 30 min later by L-DOPA (50 mg/kg), a procedure which increases brain dopamine concentrations. The flurothyl-treated rats showed a greater locomotor activity response than rats that had not been convulsed. 2 This enhanced response appears to be due to increased postsynaptic dopamine receptor sensitivity since flurothyl-treated rats also showed enhanced locomotor responses to methamphetamine (2 mg/kg) and apomorphine (2 mg/kg). 3 Enhanced 5-hydroxytryptamine-induced activity responses following administration of tranylcypromine (20 mg/kg) and L-tryptophan (50 mg/kg) were also seen 24 h after the last of 10 daily flurothyl-induced convulsions. 4 The increased 5-hydroxytryptamine response also appears to be due to increased postsynaptic sensitivity since the flurothyl-treated rats showed increased hyperactivity following administration of tranylcypromine (20 mg/kg) and the suggested 5-hydroxytryptamine agonist, 5-methoxy N,N-dimethyltryptamine (2 mg/kg). 5 No change in the brain concentration of 5-hydroxytryptamine, 5-hydroxyindoleacetic acid, tryptophan, dopamine or noradrenaline was observed 24 h after the last of 10 daily flurothyl-induced convulsions, compared to untreated rats. The rate of 5-hydroxytryptamine accumulation after tranylcypromine/L-tryptophan treatment and of dopamine and noradrenaline accumulation after tranylcypromine/L-DOPA treatment was similar in both groups. 6 Repeated flurothyl convulsion has the same effects on these behavioural tests as repeated electro-convulsive shock. Since both treatments have been used successfully to treat depression, it is suggested that the mechanism of action of electroconvulsive therapy may be by increasing postsynaptic responses to the monoamine neurotransmitters.