DOPAMINERGIC ACTIVITY AND THE DISCRIMINATIVE STIMULUS EFFECTS OF MU OPIOIDS IN PIGEONS - IMPORTANCE OF TRAINING DOSE AND ATTENUATION BY THED-3 AGONIST (+ -)-7-OH-DPAT/

The present investigation examined the effects of several dopaminergic compounds in pigeons trained to discriminate either a 0.1 (low) or 5. 6 (high) mg/kg dose of the mu opioid butorphanol from saline. Various dopamine (DA) re-uptake inhibitors, releasers, a D-1 agonist, a D-2 ag onist and a D-3 agonist engendered partial substitution (50-79% butorp hanol responding) for the butorphanol stimulus in the low-dose group. In the high-dose group, with a few exceptions, these compounds produce d predominately saline responding. In the low-dose group, the opioid a ntagonist naloxone antagonized the stimulus effects produced by butorp hanol, but failed to attenuate the butorphanol-like discriminative sti mulus effects produced by the DA re-uptake inhibitors mazindol and coc aine. The D-1 antagonist (+)-SCH 23390 and the D-2 antagonist raclopri de failed to attenuate the stimulus effects produced by either the low or high training dose of butorphanol. Doses of mazindol and cocaine t hat engendered between 16% and 70% butorphanol responding failed to al ter the butorphanol dose-effect curve in either the low-or high-dose g roup, indicating a less than additive interaction. In the high-dose gr oup, the D-3 agonist (+/-)-7-hydroxy-dipropylaminotetralin [(+/-)-7-OH -DPAT] attenuated butorphanol's stimulus effects in a dose-dependent m anner along with the butorphanol-like stimulus effects produced by nal buphine and morphine. The present ent findings indicate that direct an d indirect DA agonists share similar stimulus effects with a low but n ot high training dose of butorphanol, and in the high-training dose gr oup, activation of the D-3 receptor by (+/-)-7-OH-DPAT results in the attenuation of the discriminative stimulus effects of mu opioids.