Cardiovascular responses elicited during binge administration of cocaine.

Cocaine use is often characterized by a repeated pattern of frequent administrations (binge) followed by periods of abstinence. The repeated binge administration of methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) alters cardiovascular function and the arterial pressure and heart rate responses elicited by these drugs. Whether repeated binges of cocaine similarly affect cardiovascular function and cardiovascular responsiveness is unknown. Radiotelemetry was used to record the cardiovascular responses elicited during three successive cocaine binges (5 mg/kg, t.i.d., for 4 days) in conscious, unrestrained rats. Each binge was separated by a 10-day cocaine-free period. The effects of cocaine administration on vascular reactivity and vasovagal, Bezold-Jarisch reflex function were also evaluated. The intravenous administration of cocaine increased both mean arterial pressure (MAP) and heart rate. The arterial pressure and heart rate responses elicited by cocaine, both within and between the binges, were remarkably similar. The arterial pressure and heart rate responses elicited by the intravenous administration of sodium nitroprusside, acetylcholine and phenylephrine before each binge and 10 days after the last binge were not altered after the binge administration of cocaine. Likewise, Bezold-Jarisch reflex function elicited by intravenous serotonin was unchanged after the binge administration of cocaine. These results indicate that the administration of cocaine using this repeated binge model does not alter the arterial pressure and heart rate responses elicited by the drug, nor does it alter the cardiovascular responses elicited by a variety of vasoactive substances.

Cardiovascular responses elicited by the "binge" administration of methamphetamine.

Methamphetamine (METH) abuse is often characterized by a repeated pattern of frequent drug administrations (binge) followed by a period of abstinence. The effect of this pattern of METH use on cardiovascular function has not been characterized. Radiotelemetry was used to record the cardiovascular responses elicited during three successive METH binges (3 mg/kg, b.i.d. for 4 days) in conscious rats. Each binge was followed by a 10-day METH-free period. The effects of METH administration on vascular reactivity, Bezold-Jarisch reflex function, and cardiac morphology were also evaluated. The pressor responses elicited by the first three doses of METH in the second and third binges were significantly larger than those elicited by the corresponding doses in the first binge. The heart rate (HR) responses elicited by METH were similar within and among the three binges. Ten days after the last binge, the depressor responses elicited by the i.v. injection of sodium nitroprusside, isoproterenol, and acetylcholine were significantly smaller than those elicited before each binge. The arterial pressure and HR responses elicited by phenylephrine were unchanged. Bezold-Jarisch reflex function evoked by i.v. serotonin (10 microg/kg) was significantly altered. The hearts from treated rats showed focal inflammatory infiltrates with abundant monocytes and occasional necrotic foci. These results indicate that this binge pattern of METH administration can significantly alter cardiovascular function and cardiovascular reflex function and produce serious cardiac pathology.

Changes in cardiovascular responsiveness and cardiotoxicity elicited during binge administration of Ecstasy.

The recreational use of 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy) is often characterized by a repeated pattern of frequent drug administrations (binge) followed by a period of abstinence. Radiotelemetry was used to characterize the cardiovascular responses elicited during three MDMA binges (3 or 9 mg/kg b.i.d. for 4 days), each of which was separated by a 10-day MDMA-free period. The heart rate and mean arterial pressure (MAP) responses elicited by 3-mg/kg doses of MDMA were consistent within and between the three binges. In the first binge the 9-mg/kg doses of MDMA increased MAP and produced a biphasic (decrease/increase) heart rate response. The bradycardia elicited by MDMA in the first binge (-75 bpm) was enhanced in the second and third binges (-186 and -287 bpm, respectively). Significant hypotension accompanied the increased bradycardic responses. Atropine abolished the hypotension and significantly attenuated the bradycardic responses. The MAP and heart rate responses elicited by sodium nitroprusside, acetylcholine, phenylephrine, and serotonin (5-HT) were evaluated before each binge and 10 days after the last binge. The hypotension, but not the tachycardia elicited by sodium nitroprusside was attenuated by the repeated administration of MDMA. The responses to phenylephrine, acetylcholine, and 5-HT were unaltered after MDMA. The hearts of treated rats contained foci of inflammatory infiltrates (lymphocytes and macrophages), some of which contained necrotic cells and/or disrupted cytoarchitecture. MDMA produced cardiac arrhythmias in some rats. These results indicate that the binge administration of MDMA can significantly alter cardiovascular and cardiovascular reflex function and produce cardiac toxicity.