Effects of repeated yohimbine on the extinction and reinstatement of cocaine seeking.

Acute exposure to the pharmacological stressor yohimbine (YOH) reinstates drug seeking in rats. The present experiments investigated whether repeated exposure to YOH during extinction training affects the time-course of extinction and the magnitude of subsequent YOH- or footshock-induced reinstatement of cocaine seeking. Rats trained to self-administer cocaine were given five days of extinction training, during which they were injected with YOH (1.25 mg/kg, i.p.) either before or after daily extinction sessions. Following additional extinction training in the absence of YOH, animals were tested for reinstatement to a YOH (1.25 mg/kg, i.p.) or footshock (20 min, intermittent, 0.9 mA per 0.5 s shock) challenge. Animals injected with YOH before daily extinction sessions showed an attenuated rate of extinction, relative to control animals. Following additional extinction training in the absence of YOH treatment, these same animals showed a marked attenuation of YOH-induced reinstatement of cocaine seeking. YOH treatment during extinction did not, however, affect the magnitude of reinstatement induced by footshock. These findings demonstrate that repeated exposure to a stressor during extinction training can modulate the processes governing extinction learning and the subsequent reinstatement of drug seeking induced by that stressor.