Dynamics of extracellular dopamine in the acute and chronic actions of cocaine.
Cocaine amplifies dopaminergic neurotransmission via blockade of presynaptic neuronal uptake. This action is believed to be a crucial component of cocaine's ability to exert its reinforcing effects. This review will provide a brief overview of extracellular dopamine dynamics associated with cocaine. The acute effects of cocaine reviewed include comparison of intravenous and intraperitoneal routes of administration to better understand how fast and slow routes (e.g., crack and intranasal) differ in their pharmacokinetics and neurochemical effects and how those differences relate to differences in abuse potential. Changes in the acute effects of cocaine within a session have been examined in neurochemical studies of acute tolerance to self-administered cocaine in rhesus monkeys, and the potential impact of that tolerance to patterns of use is discussed. Between-session sensitization of the dopaminergic response to cocaine is reviewed, and data indicating this also occurs in primates have been obtained in self-administering rhesus monkeys, demonstrating neurochemical sensitization in a primate species. The important question of whether cocaine-associated environmental cues elicit conditioned increases in dopamine release has also been examined in the rhesus monkey, with results indicating that, unlike rats, nonhuman primates do not show conditioned increases in dopamine release.
Departments of Psychiatry and Laboratory Medicine, West Haven Veterans Administration Hospital, Yale University School of Medicine, WHVA/116A2, 950 Campbell Avenue, West Haven, CT 06516, USA. charles.bradberry@yale.edu
Charles W
CW
Bradberry
D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D003042:Cocaine / Q000493:pharmacokinetics / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000378:metabolism; D003213:Conditioning, Psychological / Q000187:drug effects; D003463:Cues; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D004361:Drug Tolerance; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D012054:Reinforcement, Psychology; D012646:Self Administration
D018765:Dopamine Uptake Inhibitors; D003042:Cocaine; D004298:Dopamine