Abstract
Several agents may treat cocaine addiction and toxicity including bromocriptine, desipramine, GBR 12909 [1-(2-(bis(4-fluorphenyl)-methoxy)-ethyl)-4-(3-phenyl-propyl)piperazine], diazepam, buprenorphine and dizocilpine. In this study, we sought to determine whether these specific therapeutic agents alter cardiovascular responses to cocaine in conscious rats. Arterial pressure responses to cocaine (5 mg/kg, i.v.) were similar in all rats whereas cardiac output responses varied widely. In 26 of 33 rats (named vascular responders), cocaine induced a decrease in cardiac output of 8% or more. The remaining rats with little change or an increase in cardiac output were classified as mixed responders. Pretreatment with bromocriptine (0.1 mg/kg) or desipramine (1 mg/kg) increased cardiac output in mixed responders and increased systemic vascular resistance in vascular responders similar to the differential effects noted with cocaine. 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 effects 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 difference in cardiac output responses in vascular and mixed responders by reducing the cocaine-induced decrease in cardiac output in vascular responders. 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 enhanced the increase in systemic vascular resistance whereas dizocilpine enhanced the pressor response. These data suggest that several treatment regimens for cocaine addiction alter the cardiovascular responses to cocaine and that dopamine D2 receptor activation may be necessary for the decrease in cardiac output noted in vascular responders.
Footnotes
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Send reprint requests to: Dr. Mark M. Knuepfer, Department of Pharmacological and Physiological Science, St. Louis University School of Medicine, 1402 S. Grand Boulevard, St. Louis, MO 63104.
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↵1 These studies were supported by United States Public Health Service Grant DA-05180.
- Abbreviations:
- ANOVA
- analysis of variance
- Brc
- bromocriptine
- Bup
- buprenorphine
- COC
- cocaine hydrochloride
- CHG
- change
- CO
- cardiac output
- Des
- desipramine
- Dzp
- diazepam
- GBR 12909 or GBR
- 1-(2-(bis(4-fluorphenyl)-methoxy)-ethyl)-4-(3-phenyl-propyl)piperazine
- HR
- heart rate
- INJ
- injection
- MAP
- mean arterial pressure
- MK-801 or MK8
- dizocilpine
- NMDA
- N-methyl-d-aspartic acid
- SV
- stroke volume
- SysVR
- systemic vascular resistance
- Received February 25, 1997.
- Accepted July 11, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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