Alpha-2 adrenergic receptor agonists block stress-induced reinstatement ofcocaine seeking

The alpha-2 adrenergic receptor agonists, cloindine, lofexidine and guanabe nz, blocked stress- but not cocaine-induced reinstatement of cocaine seekin g at doses that suppressed footshock-induced release of noradrenaline in pr efrontal 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 d ays), were returned to the self-administration chambers for daily extinctio n and reinstatement test sessions. Both intermittent footshock (15 min, 0.6 IIIA) and cocaine priming (20 mg/kg, i.p.) reinstated extinguished drug se eking. Pretreatment with either clonidine (20, or 40 mu g/kg, i.p.) or lofe xidine (50, 100, 150, or 200 mu g/kg, i.p.) attenuated footshock- but not c ocaine-induced reinstatement of cocaine seeking. Guanabenz (640 mu g/kg, ip ) an alpha-2 agonist with low affinity for imidazoline type-1 receptors, al so attenuated footshock- but but not cocaine-induced reinstatement of cocai ne seeking. The results point to an important role for NE systems in the ef fects of footshock on relapse to cocaine seeking. (C) 2000 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. All rights reserved.