Reinstatement of cocaine seeking in rats by the pharmacological stressors, corticotropin-releasing factor and yohimbine: role for D1/5 dopamine receptors.
BACKGROUND
Two pharmacological stressors commonly used in the study of stress-induced reinstatement of drug seeking are central injections of the stress peptide, corticotropin-releasing factor (CRF), and systemic administration of the α(2)-adrenoceptor antagonist, yohimbine. Despite the widespread use of these stressors, the neurochemical systems mediating their ability to reinstate cocaine-seeking behaviour have not been fully characterized.


OBJECTIVE
The present study was designed to characterize the role, specifically, of dopamine transmission in the reinstating effects of CRF and yohimbine on cocaine seeking.


METHODS
Male Long-Evans rats were trained to self-administer cocaine (0.23 mg/kg/infusion) for 8-10 days. Subsequently, responding for drug was extinguished, and tests for CRF- (0.5 μg; i.c.v.) and yohimbine-induced (1.25 mg/kg; i.p.) reinstatement were conducted following pretreatment with the dopamine D1/5 receptor antagonists, SCH23390 (0.05, 0.1 mg/kg; i.p.) and/or SCH31966 (0.2 mg/kg; i.p.), and the D2/3 receptor antagonist, raclopride (0.25, 0.5 mg/kg; i.p.).


RESULTS
Pretreatment with SCH23390, but not raclopride, blocked CRF-induced reinstatement of cocaine seeking. Pretreatment with SCH23390 and SCH31966, but not raclopride, blocked yohimbine-induced reinstatement of cocaine seeking.


CONCLUSIONS
These findings demonstrate that transmission at D1/5, but not D2/3, receptors mediates the reinstatement of cocaine seeking induced by CRF and yohimbine.
Department of Psychology, Centre for the Neurobiology of Stress, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4, Canada.
Z J
ZJ
Brown
D A
DA
Kupferschmidt
Suzanne
S
Erb
D058669:Adrenergic alpha-2 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D016739:Behavior, Addictive / Q000378:metabolism / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000378:metabolism* / Q000517:prevention & control / Q000523:psychology; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D005108:Extinction, Psychological / Q000187:drug effects; D057967:Infusions, Intraventricular; D007263:Infusions, Parenteral; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000187:drug effects / Q000378:metabolism*; D012008:Recurrence; D012646:Self Administration; D013395:Sucrose / Q000008:administration & dosage; D013997:Time Factors; D015016:Yohimbine / Q000008:administration & dosage / Q000494:pharmacology*
D058669:Adrenergic alpha-2 Receptor Antagonists; D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; C493595:Drd3 protein, rat; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D015016:Yohimbine; D013395:Sucrose; D003346:Corticotropin-Releasing Hormone; D003042:Cocaine