Nicotine and heroin augment cocaine-induced dopamine overflow in nucleus accumbens.
The current public debate on nicotine concentrates on the abuse potential of nicotine per se. However, little is known about the interaction of nicotine with other drugs of well-established abuse liability such as cocaine. Indeed, cigarette smoking increases the intake of cocaine and other drugs of abuse. In order to test if these epidemiological data are reflected in a neurochemical correlate of the reinforcing effects of drugs of abuse, i.e., dopamine overflow in the nucleus accumbens, in vivo brain microdialysis was used to examine the effects of nicotine and cocaine either alone or in combination in freely moving rats. Furthermore, the effects of the nicotine + cocaine combination were compared to another drug combination of high abuse potential, i.e., heroin + cocaine ('speedball'). Both nicotine + cocaine as well as heroin + cocaine stimulated nucleus accumbens dopamine overflow in an additive manner. Repeated intermittent administration of nicotine did not significantly alter the effects of a subsequent challenge with the nicotine + cocaine combination. These data suggest that the clinical-epidemiological findings on either drug combination are reflected in a stimulatory interaction on nucleus accumbens dopamine overflow that is additive. No significant tolerance seems to develop to this effect of nicotine. These neurochemical findings support behavioral data suggesting that the reinforcing effects of cocaine and heroin are additive and predict that nicotine will enhance the reinforcing effects of cocaine.
Zernig
G
G
Department of Psychiatry, University of British Columbia, Vancouver, Canada. gerald.zernig@kfunigraz.ac.at
O'Laughlin
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IA
Fibiger
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HC
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D003932:Heroin / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009294:Narcotics / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D009294:Narcotics; D018722:Nicotinic Agonists; D015102:3,4-Dihydroxyphenylacetic Acid; D009538:Nicotine; D003932:Heroin; D003042:Cocaine; D004298:Dopamine; D006719:Homovanillic Acid