Behavioural studies of the actions of cocaine, monoamine oxidase inhibitors and iminodibenzyl compounds on central dopamine neurones

Abstract

1 Turning behaviour after unilateral lesions of the nigro-striatal dopamine pathway in rats has been used to compare the actions of cocaine and desipramine on central dopamine-containing neurones. 2 Administration of cocaine alone (5–20 mg/kg) resulted in no turning or minimal turning towards the lesioned side; the monoamine oxidase inhibitors nialamide and pargyline administered alone were also ineffective. 3 After pre-treatment with nialamide (100 mg/kg) or pargyline (25 mg/kg) cocaine evoked high rates of turning towards the lesioned side. 4 Desipramine (1–100 mg/kg), either alone or in combination with nialamide did not evoke turning. 5 Turning evoked by the cocaine-nialamide combination was abolished by pre-treatment with α-methyl-p-tyrosine (150 mg/kg). 6 Pre-treatment with reserpine (5 mg/kg, 24 h previously) substantially diminished turning evoked by the cocaine-nialamide combination but potentiated turning resulting from administration of methylamphetamine (5 mg/kg). 7 Cocaine (20 mg/kg) administered 15 min prior to (+)-methylamphetamine (5 mg/kg) reduced the turning behaviour in the first hour after administration of the latter drug but prolonged the total duration of the effect.