Role of the central nervous system in hemodynamic and sympathoadrenal responses to cocaine in rats.
These studies were undertaken to examine the contribution of central nervous system mechanisms to the cardiovascular and sympathoadrenal effects of cocaine. Changes in systolic and diastolic blood pressure, heart rate and plasma catecholamine concentrations were determined in response to cocaine injected i.a. or i.c.v. in conscious unrestrained rats. Systemically administered cocaine produced brisk, transient dose-related increases in systolic and diastolic pressure at doses of 0.05 to 5 mg/kg i.a. Plasma catecholamine concentrations increased in a dose-related manner, reaching peak levels at 5 to 10 min after i.a. cocaine injection. Only the higher doses of cocaine induced reflex vagal bradycardia that was blocked by atropine (0.4 mg/kg i.a.). Propranolol (1 mg/kg i.a.) prolonged the duration of cocaine-induced hypertension and bradycardia. Ganglionic blockade with chlorisondamine (7.5 mg/kg i.a.) antagonized completely the cardiovascular and sympathoadrenal effects of cocaine, indicating that intact ganglionic transmission is required for full expression of the autonomic responses. Antagonist drugs selective for the D-1 or D-2 dopamine receptors attenuated effects of cocaine on plasma catecholamine concentrations but not on cardiovascular parameters. Intracerebroventricular injection of cocaine (50-250 micrograms) increased systolic pressure and plasma catecholamine concentrations, providing direct evidence for an action of cocaine in the central nervous system. These results demonstrate that cocaine acts centrally to increase sympathetic outflow leading to hypertension and reflex bradycardia in conscious rats.
Department of Neurology, University of Michigan, Ann Arbor.
J A
JA
Kiritsy-Roy
J B
JB
Halter
S M
SM
Gordon
M J
MJ
Smith
L C
LC
Terry
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D002395:Catecholamines / Q000097:blood*; D002714:Chlorisondamine / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000502:physiology; D012457:Salicylamides / Q000494:pharmacology
D001552:Benzazepines; D002395:Catecholamines; D011954:Receptors, Dopamine; D012457:Salicylamides; D001285:Atropine; D011433:Propranolol; D003042:Cocaine; C045989:eticlopride; D002714:Chlorisondamine