Pre-drug cues modulate morphine tolerance, striatal c-Fos, and AP-1 DNA binding

To evaluate the molecular mechanisms that mediate the effect of learning on morphine tolerance in rats, we examined striatal c-Fos, and c-Jun protein expression, and AP-I DNA binding. Morphine paired with a conditioned stimul us (CS) led to analgesic tolerance in the presence of the CS. Rats receivin g morphine unpaired with the CS displayed significantly less tolerance than paired morphine animals. Striatal c-Fos protein levels and AP-I DNA bindin g activity were increased in rats receiving paired morphine compared with r ats that did not receive morphine but not in rats receiving morphine withou t the CS. No differences were found in c-Jun levels. These results suggest that Pavlovian conditioning may account, in part, for the molecular mechani sms associated with morphine tolerance. (C) 1998 Lippincott Williams & Wilk ins.