EFFECTS OF PROPOSED TREATMENTS FOR COCAINE ADDICTION ON HEMODYNAMIC RESPONSIVENESS TO COCAINE IN CONSCIOUS RATS

Several agents may treat cocaine addiction and toxicity including brom ocriptine, desipramine, GBR 12909 l)-methoxy)-ethyl)-4-(3-phenyl-propy l)piperazine], diazepam, buprenorphine and dizocilpine. In this study, we sought to determine whether these specific therapeutic agents alte r cardiovascular responses to cocaine in conscious rats. Arterial pres sure responses to cocaine (5 mg/kg, i.v.) were similar in all rats whe reas cardiac output responses varied widely. In 26 of 33 rats (named v ascular responders), cocaine induced a decrease in cardiac output of 8 % or more. The remaining rats with little change or an increase in car diac output were classified as mixed responders. Pretreatment with bro mocriptine (0.1 mg/kg) or desipramine (1 mg/kg) increased cardiac outp ut in mixed responders and increased systemic vascular resistance in v ascular responders similar to the differential effects noted with coca ine. GBR 12909 (0.5-10 mg/kg) elicited a decrease in cardiac output at higher doses. Diazepam (0.1 and 0.5 mg/kg) had small, short-lasting e ffects on cardiovascular parameters. Buprenorphine (0.3 mg/kg) or the NMDA (N-methyl-D-aspartic acid) receptor antagonist, dizocilpine (0.05 mg/kg), increased arterial pressure, heart rate and cardiac output in Vascular responders. Bromocriptine and desipramine prevented the diff erence in cardiac output responses in vascular and mixed responders by reducing the cocaine-induced decrease in cardiac output in vascular r esponders. Pretreatment with GBR 12909 (1 mg/kg) had little effect on cardiovascular responses to cocaine except to depress the increase in cardiac output noted in mixed responders. Buprenorphine selectively en hanced the increase in systemic vascular resistance whereas dizocilpin e enhanced the presser response. These data suggest that several treat ment regimens for cocaine addiction alter the cardiovascular responses to cocaine and that dopamine D-2 receptor activation may be necessary for the decrease in cardiac output noted in vascular responders.