Figure 1.

Stimulation of α₂ adrenergic receptors blocked cue-induced reinstatement of extinguished cocaine-seeking. (A) The mixed α₂/ imidazoline-1 (I₁) receptor agonist clonidine significantly attenuated cue-induced reinstatement of active lever pressing at 20 μg/kg (n=15), but not 5 μg/kg (n=8) or10 μg/kg (n=7), as compared to vehicle (***p<0.001). Extinction (ext) levels of responding prior to reinstatement are also shown. (B) Pretreatment with the selective α₂ antagonist RS-79948 (1 mg/kg) blocked the effects of 20 μg/kg clonidine on cue-induced reinstatement (n=10; *p<0.05, as compared to 0/0 vehicle condition). (C) RS-79948 alone did not trigger reinstatement when administered prior to an extinction session (ext; n=8), and did not potentiate cue-induced reinstatement (cues; n=9). (D) Acute clonidine reduced cocaine-seeking on the first day of extinction (n=8 and 8; ***p<0.001). Clonidine- and vehicle-treated rats were not significantly different on subsequent extinction days when no pretreatment was given. (E) The selective α₂ agonist UK-14,304 significantly attenuated cue-induced reinstatement at 200 μg/kg (n=6), but not 50 or 100 μg/kg (n=12), as compared to vehicle (**p<0.01). (F) The selective α_2A agonist guanfacine significantly attenuated cue-induced reinstatement at 1 mg/kg, but not 0.2 mg/kg (n=9), as compared to vehicle (*p<0.05).