Stress-induced reinstatement of cocaine seeking is mediated by the kappa opioid system.
BACKGROUND
Prior activation of the kappa opioid system by repeated stress or agonist administration has been previously shown to potentiate the rewarding properties of subsequently administered cocaine. In the present study, intermittent and uncontrollable footshock, a single session of forced swim, or acute administration of the kappa agonist U50,488 (5 mg/kg) were found to reinstate place preference in mice previously conditioned with cocaine (15 mg/kg) and subsequently extinguished by repeated training sessions without drug.


CONCLUSIONS
Stress-induced reinstatement did not occur for mice pretreated with the kappa opioid receptor antagonist norbinaltorphimine (10 mg/kg) and did not occur in mice lacking either kappa opioid receptors (KOR -/-) or prodynorphin (Dyn -/-). In contrast, the initial cocaine conditioning and extinction rates were not significantly affected by disruption of the kappa opioid system. Cocaine-injection also reinstated conditioned place preference in extinguished mice; however, cocaine-primed reinstatement was not blocked by kappa opioid system disruption.


CONCLUSIONS
The results suggest that stress-induced drug craving in mice may require activation of the dynorphin/kappa opioid system.
Department of Pharmacology, University of Washington, 1959 NE Pacific St., Seattle, WA 98185-7280, USA.
Van A
VA
Redila
Charles
C
Chavkin
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D003216:Conditioning, Operant / Q000187:drug effects*; D004195:Disease Models, Animal; D004745:Enkephalins / Q000235:genetics; D005108:Extinction, Psychological; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011498:Protein Precursors / Q000235:genetics; D017473:Receptors, Opioid, kappa / Q000187:drug effects* / Q000235:genetics; D013315:Stress, Psychological / Q000503:physiopathology*; D013550:Swimming
D004745:Enkephalins; D011498:Protein Precursors; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C033660:preproenkephalin