title: Central mechanisms of action involved in cocaine-induced tachycardia.
abstract: The present study was designed to determine the central effects of cocaine on heart rate and blood pressure in Wistar Kyoto rats (WKY) and to evaluate mechanisms involved in the response. Cocaine (0.025-4 mg/kg) was administered to unanesthetized, unrestrained rats via a cannula placed into the lateral ventricle. Procaine (0.1 and 4 mg/kg) was also administered centrally. Cocaine did not significantly alter blood pressure at doses of 0.025, 0.1, or 0.5 mg/kg, icv. Only the highest dose, 4 mg/kg, icv produced a significant pressor response. Cocaine produced significant dose-dependent tachycardia, with the maximum increase in heart rate occurring within 5 min. Procaine (4 mg/kg, icv) produced tachycardia, but the effect was significantly less than that produced by cocaine (4 mg/kg, icv). Cocaine also produced tachycardia at a dose of 0.1 mg/kg, but procaine did not significantly alter heart rate at the same dose. Central phentolamine pretreatment (0.1 mg/kg, icv) significantly attenuated the increase in heart rate produced by cocaine. These results indicate that the centrally mediated tachycardia produced by cocaine is partly due to its local anesthetic activity and to indirect stimulation of alpha receptors.
authors.affiliation: Cardiovascular Pharmacodynamics Laboratory, College of Pharmacy, University of Georgia, Athens 30602.
authors.forename: L F
authors.initials: LF
authors.lastname: Jones
authors.forename: R L
authors.initials: RL
authors.lastname: Tackett
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003042:Cocaine / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D011343:Procaine / Q000633:toxicity; D051381:Rats; D011921:Rats, Inbred WKY; D013610:Tachycardia / Q000139:chemically induced*
chemical_list: D011343:Procaine; D003042:Cocaine