MONOAMINE TRANSPORTER AND SODIUM-CHANNEL MECHANISMS IN THE RAPID PRESSOR-RESPONSE TO COCAINE

Intravenous (IV) cocaine (0.03-3 mg/kg) produced dose-dependent, rapid , and brief increases in blood pressure (BP) in conscious rats pretrea ted with the dopamine receptor antagonist, SCH 23390, Monoamine uptake inhibitors structurally analogous to cocaine (cocaethylene, CFT, beta CIT, CPT, (+)-cocaine, norcocaine, and benztropine) also produced thi s rapid presser response, whereas structurally unrelated uptake inhibi tors with diverse monoamine transporter selectivities (BTCP, indatrali ne, GBR 12935, mazindol, nomifensine, and zimeldine) either did not pr oduce a rapid presser response or produced only a small presser respon se. At nonconvulsant doses, the sodium channel blockers acetylprocaina mide, dibucaine, dyclonine, prilocaine, proparacaine, quinidine, and t etracaine produced a small presser response or no increase in BP. In r ats implanted with telemetric devices, cocaine and its analog, CFT, pr oduced a biphasic pharmacological response that consisted of an initia l brief and abrupt behavioral arousal associated with a rapid; large i ncrease in BP followed by prolonged, parallel increases in BP and loco motor activity. Pretreatment with SCH 23390 prevented the prolonged bu t not the initial rapid and brief presser and activity responses to bo th cocaine and CFT. administration. The present data suggest that the inhibition of dopamine, norepinephrine, or serotonin transporter funct ions, either alone or in combination, does not mediate the rapid press er response to cocaine. The sodium channel-blocking action of cocaine per se does not appear to be involved in the rapid presser response to cocaine. Finally, the present results confirm previous findings that dopaminergic mechanisms mediate the prolonged increases in BP and loco motor activity produced by cocaine. (C) 1998 Elsevier Science Inc.