Morphine as a discriminative stimulus: role of periaqueductal gray neurons.

The present study investigated the degree of involvement of the periaqueductal gray (PAG) in the mediation of the discriminative stimulus (DS) effects of morphine sulfate (MS). Eleven rats were trained to discriminate MS (3 mg/kg; s.c.) from saline (1 ml/kg; s.c.) using a two-bar operant procedure. After the rats learned the discrimination to the criterion of 80% correct responding, cannulae were unilaterally implanted into the PAG. Intracerebral (i.c.) injection of MS (1 microliter) into the PAG produced stimulus control similar to that observed following systemic MS. Doses of 0.5, 1.0, 2.0 and 4.0 microgram elicited MS-correct responding of 27, 57, 63 and 77% respectively. The highest intraPAG MS dose elicited significantly more MS correct responding than did either systemic or the i.c. injection of saline, while not differing from systemically-administered MS. These results suggest that the PAG may at least be partially responsible for the generation of morphine's DS effect when administered s.c.