COCAINE-INDUCED ELEVATION OF PLASMA-CORTICOSTERONE IS MEDIATED BY DIFFERENT NEUROTRANSMITTER SYSTEMS IN RATS

It has previously been demonstrated that cocaine stimulates the hypoth alamic-pituitary-adrenal (HPA) axis through hypothalamic corticotropin -releasing factor (CRF) secretion. The role of different neurotransmit ters in mediation of the cocaine-induced elevation of plasma corticost erone (CORT) were investigated in rats by using transmitter antagonist s . Peripheral (IP) pretreatment with a dopaminergic antagonist, pimoz ide (0.01-1.0 mg/kg, IP), a noradrenergic blocker, phenoxybenzamine (1 .0-4.0 mg/kg, IP), a beta-adrenergic blocker, propranolol (0.2- 10 mg/ kg, IP), an opiate antagonist, naloxone (1.0-4.0 mg/kg, IP), and a mus carinic cholinergic antagonist, atropine (1.0-4.0 mg/kg, IP), inhibite d the cocaine-induced CORT response dose dependently. A similar dose-d ependent inhibition of the plasma CORT response induced by cocaine was observed after the ICV route of administration of these antagonists i n microgram quantities. None of the investigated IP or ICV doses of tr ansmitter antagonists altered the basal CORT level. These results sugg est that the activation of multiple neurotransmitter systems, includin g catecholaminergic, opiate, and cholinergic systems, might be respons ible for the cocaine-induced HPA axis activation, probably through the specific receptors located in the CNS.