Aminergic influences on intravenous cocaine self-administration by rhesus monkeys

It is demonstrated that agents known to alter central aminergic systems affect cocaine self-administration and tends to implicate either dopamine or norepinephrine as mediators of either cocaine-based reinforcement or of the other effects of cocaine which may regulate the frequency of its administration.

Abstract

Earlier observations have demonstrated that when allowed limited daily access to cocaine, monkeys self-administer approximately the same amount of cocaine daily. Treatment with neuroleptic agents increases the frequency of this behavior which could be interpreted as resulting from an antagonism of the reinforcing actions of cocaine. The present paper demonstrates that agents known to alter central aminergic systems affect cocaine self-administration. Acute treatment with pargyline (50 and 100 mg/kg) decreased the behavior; DL alpha-methylparatyrosine (50 mg/kg) increased the behavior. Treatment with the peripheral alpha adrenergic blocking agents phentolamine and phenoxybenzamine (0.5 - 8.0 mg/kg) did not significantly alter the behavior. Chronic treatment (5-10 days) with reserpine (0.1 - 1.0 mg/kg) produced an initial increase in self-administration to which tolerance developed. Upon discontinuation of reserpine treatment, cocaine self-administration was decreased below baseline levels. Results tend to implicate either dopamine or norepinephrine as mediators of either cocaine-based reinforcement or of the other effects of cocaine which may regulate the frequency of its administration. Results were discussed in relation to those obtained from clinical studies in which drug effects on amphetamine-induced euphoria were ascertained.