Dopaminergic activity and the discriminative stimulus effects of mu opioids in pigeons:: importance of training dose and attenuation by the D3 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 agonist and a D-3 agonist engendered partial substitution (50-79% butorphanol responding) for the butorphanol stimulus in the low-dose group. In the high-dose group, with a few exceptions, these compounds produced predominately saline responding. In the low-dose group, the opioid antagonist naloxone antagonized the stimulus effects produced by butorphanol, but failed to attenuate the butorphanol-like discriminative stimulus effects produced by the DA re-uptake inhibitors mazindol and cocaine. The D-1 antagonist (+)-SCH 23390 and the D-2 antagonist raclopride failed to attenuate the stimulus effects produced by either the low or high training dose of butorphanol. Doses of mazindol and cocaine that engendered between 16% and 70% butorphanol responding failed to alter the butorphanol dose-effect curve in either the low-or high-dose group, indicating a less than additive interaction. In the high-dose group, the D-3 agonist (+/-)-7-hydroxy-dipropylaminotetralin [(+/-)-7-OH-DPAT] attenuated butorphanol's stimulus effects in a dose-dependent manner along with the butorphanol-like stimulus effects produced by nalbuphine and morphine. The present ent findings indicate that direct and indirect DA agonists share similar stimulus effects with a low but not high training dose of butorphanol, and in the high-training dose group, activation of the D-3 receptor by (+/-)-7-OH-DPAT results in the attenuation of the discriminative stimulus effects of mu opioids.