Pharmacological and environmental determinants of relapse to cocaine-seeking behavior.
Animal models have been developed that simulate relevant features of relapse to cocaine-seeking behavior in humans. These models have provided valuable information about pharmacological and environmental factors that precipitate reinstatement of extinguished cocaine-seeking in rats and monkeys, as well as new insights about potential pharmacotherapies for relapse prevention. Reinstatement of cocaine-seeking behavior in animals can be induced by cocaine priming or by cocaine-paired environmental stimuli: however, maximum reinstatement of drug-seeking appears to be induced when cocaine priming and cocaine-paired stimuli are combined. Drugs that share cocaine's indirect dopamine agonist properties or that act as direct agonists at D2-like dopamine receptors also induce reinstatement of cocaine-seeking behavior, whereas with some exceptions (e.g., caffeine, morphine) drugs from other pharmacological classes do not. D1-like receptor agonists block rather than mimic the priming effects of cocaine, suggesting different roles for D1- and D2-like receptor mechanisms in cocaine relapse. Although considerable overlap exists, drugs that exhibit cocaine-like discriminative stimulus and/ or reinforcing effects in other situations do not invariably induce cocaine-like reinstatement of drug-seeking and vice versa, implying that these effects are not simply different behavioral expressions of a unitary neurobiological process. Finally, recent findings with D1-like receptor agonists, partial agonists, and antagonists suggest that some of these drugs may be viable candidates for development as antirelapse pharmacotherapies.
Spealman
R D
RD
Harvard Medical School, New England Regional Primate Research Center, Southborough, MA 01772-9102, USA.
Barrett-Larimore
R L
RL
Rowlett
J K
JK
Platt
D M
DM
Khroyan
T V
TV
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000523:psychology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D006801:Humans; D051381:Rats; D012008:Recurrence; D012931:Social Environment
D018765:Dopamine Uptake Inhibitors; D003042:Cocaine