Neurochemical changes in cocaine withdrawal.
Cocaine withdrawal in animals causes a transient increase followed by a long-lasting decrease in mesolimbic dopamine transporters, dopamine efflux and the number of dopamine cells firing spontaneously. Other changes in the nucleus accumbens and frontal cortex also suggest alterations in dopamine-receptive neurones and circuits. In humans, brain imaging has provided evidence for some similar, long-lasting changes in dopaminergic neurones and innervated areas. These results suggest a protracted biochemical abstinence syndrome for cocaine. In this review, Michael Kuhar and Nancy Pilotte focus on biochemical changes that occur following withdrawal from repeated cocaine administration. A key question for treatment is whether (some of) these persistent changes underlie withdrawal symptomatology such as anhedonia and relapse.
Kuhar
M J
MJ
Yerkes Regional Primate Research Center, Emory University, Atlanta, GA 30322, USA.
Pilotte
N S
NS
D000818:Animals; D001923:Brain Chemistry; D003042:Cocaine / Q000009:adverse effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D015195:Drug Design; D005625:Frontal Lobe / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009714:Nucleus Accumbens / Q000166:cytology / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism
D003042:Cocaine; D004298:Dopamine