Cocaine-induced elevation of plasma corticosterone is mediated by different neurotransmitter systems in rats.
It has previously been demonstrated that cocaine stimulates the hypothalamic-pituitary-adrenal (HPA) axis through hypothalamic corticotropin-releasing factor (CRF) secretion. The role of different neurotransmitters in mediation of the cocaine-induced elevation of plasma corticosterone (CORT) were investigated in rats by using transmitter antagonists. Peripheral (IP) pretreatment with a dopaminergic antagonist, pimozide (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 muscarinic cholinergic antagonist, atropine (1.0-4.0 mg/kg, IP), inhibited the cocaine-induced CORT response dose dependently. A similar dose-dependent inhibition of the plasma CORT response induced by cocaine was observed after the ICV route of administration of these antagonists in microgram quantities. None of the investigated IP or ICV doses of transmitter antagonists altered the basal CORT level. These results suggest that the activation of multiple neurotransmitter systems, including catecholaminergic, opiate, and cholinergic systems, might be responsible for the cocaine-induced HPA axis activation, probably through the specific receptors located in the CNS.
Sarnyai
Z
Z
Institute of Pathophysiology, Albert Szent Györgyi Medical University, Szeged, Hungary.
Bíró
E
E
Telegdy
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G
D000818:Animals; D001285:Atropine / Q000008:administration & dosage / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D008297:Male; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000502:physiology*; D010643:Phenoxybenzamine / Q000008:administration & dosage / Q000494:pharmacology; D010868:Pimozide / Q000008:administration & dosage / Q000494:pharmacology; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D018377:Neurotransmitter Agents; D010643:Phenoxybenzamine; D010868:Pimozide; D009270:Naloxone; D001285:Atropine; D011433:Propranolol; D003042:Cocaine; D003345:Corticosterone