Alpha-2 adrenergic receptor agonists block stress-induced reinstatement of cocaine seeking.
The alpha-2 adrenergic receptor agonists, clonidine, lofexidine and guanabenz, blocked stress- but not cocaine-induced reinstatement of cocaine seeking at doses that suppressed footshock-induced release of noradrenaline in prefrontal cortex and amygdala. Rats were trained to self-administer cocaine (0.5 mg/kg/infusion, i.v; 10-12 days) and, after a drug-free period (7-13 days), were returned to the self-administration chambers for daily extinction and reinstatement test sessions. Both intermittent footshock (15 min, 0.6 mA) and cocaine priming (20 mg/kg, i.p.) reinstated extinguished drug seeking. Pretreatment with either clonidine (20, or 40 microg/kg, i.p.) or lofexidine (50, 100, 150, or 200 microg/kg, i.p.) attenuated footshock- but not cocaine-induced reinstatement of cocaine seeking. Guanabenz (640 microg/kg, i.p.), an alpha-2 agonist with low affinity for imidazoline type-1 receptors, also attenuated footshock- but not cocaine-induced reinstatement of cocaine seeking. The results point to an important role for NE systems in the effects of footshock on relapse to cocaine seeking.
Erb
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Center for Studies in Behavioral Neurobiology, Department of Psychology, Concordia University, Quebec, Montreal, Canada.
Hitchcott
P K
PK
Rajabi
H
H
Mueller
D
D
Shaham
Y
Y
Stewart
J
J
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000627:therapeutic use*; D000818:Animals; D002404:Catheterization; D003000:Clonidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D003042:Cocaine / Q000008:administration & dosage; D019970:Cocaine-Related Disorders / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006143:Guanabenz / Q000008:administration & dosage; D007262:Infusions, Intravenous; D007274:Injections, Intraperitoneal; D008297:Male; D017551:Microdialysis; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D009638:Norepinephrine / Q000032:analysis / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D012646:Self Administration; D013312:Stress, Physiological / Q000150:complications* / Q000503:physiopathology; D013395:Sucrose / Q000008:administration & dosage
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D009292:Narcotic Antagonists; D013395:Sucrose; D006143:Guanabenz; D003042:Cocaine; D003000:Clonidine; C025655:lofexidine; D009638:Norepinephrine