Autonomic mechanisms in the acute cardiovascular effects of cocaine in conscious rats

We studied the differential involvement of central dopaminergic activation and autonomic nervous system regulatory mechanisms in the cardiovascular re sponses to cocaine in conscious rats. Sprague-Dawley rats, Wistar-Kyoto rat s (WKY) and spontaneously hypertensive rats (SHR) were instrumented with ca theters in the jugular vein and abdominal aorta at least 5 days before the experiment. Intravenous administration of cocaine (0.1-3.0 mg/kg) caused a dose-dependent increase in blood pressure that was biphasic, with a large a nd rapid increase peaking at 10 s, followed by a mild sustained presser res ponse. Presser responses to cocaine were significantly greater in SHR when compared to WKY rats. However, pretreatment with dopamine D-1 receptor anta gonist SCH 23390 or the D-2 receptor antagonist raclopride did not influenc e the effects of cocaine. Pretreatment with the a-adrenoceptor antagonist p hentolamine or the ganglion blocker pentolinium blocked the peak response a nd reversed the more sustained response into a depressor effect. While pret reatment with propranolol alone did not alter the responses to cocaine, in rats pretreated with phentolamine and propranolol neither a presser respons e nor a depressor response was observed. In conclusion, cocaine administrat ion caused marked, but short lasting presser responses that were mediated b y sympathetic activation and alpha-adrenoceptor vasoconstriction with littl e involvement of central dopaminergic mechanisms. The rapid return of blood pressure towards baseline may be mediated by sympathoinhibition and beta-a drenoceptor-mediated vasodilatation, the latter of which being particularly prominent when oc-adrenoceptor activation was prevented. (C) 1998 Elsevier Science B.V. All rights reserved.