Molecular mechanisms associated with cocaine effects. Possible relationships with effects of ethanol.
Cocaine has been shown to be a highly addictive and toxic drug. It produces these effects and a variety of other physiological and behavioral effects through its interactions with several distinct central nervous system receptor sites. We present the results of a series of studies that utilized multiple site analyses to elucidate which cocaine binding sites influence the reinforcing and toxic effects of cocaine and with what proportion of influence. The nature of cocaine interactions with monoamine transporters is also discussed, especially with the dopamine transporter, which has been shown to be the cocaine binding site that is primarily associated with the reinforcing effects of cocaine. We also provide evidence that vulnerability to both the toxic and addictive effects of cocaine may be significantly influenced by genetic differences in both humans and animals. In view of the fact that cocaine is commonly abused in a polydrug situation, we present the results of both behavioral and biochemical experiments which suggest that common biochemical pathways may mediate the reinforcing or addictive properties of drugs of abuse. Finally, we discuss research on the biochemical mechanisms associated with effects of ethanol, particularly those which may also influence cocaine self-administration and speculate on pharmacotherapeutic strategies for concurrent abuse of cocaine and ethanol.
Preclinical Pharmacology Branch, National Institute on Drug Abuse, Addiction Research Center, Baltimore, Maryland 21224.
M C
MC
Ritz
M J
MJ
Kuhar
F R
FR
George
D000437:Alcoholism / Q000235:genetics / Q000503:physiopathology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D003042:Cocaine / Q000009:adverse effects* / Q000493:pharmacokinetics; D000431:Ethanol / Q000009:adverse effects* / Q000493:pharmacokinetics; D006801:Humans; D018377:Neurotransmitter Agents / Q000378:metabolism*; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000502:physiology; D012307:Risk Factors; D019966:Substance-Related Disorders / Q000235:genetics / Q000503:physiopathology*
D018377:Neurotransmitter Agents; D017981:Receptors, Neurotransmitter; D000431:Ethanol; D003042:Cocaine