Dopamine receptors in the ventral pallidum regulate circling induced by opioids injected into the ventral pallidum

Abstract

Recent reports have indicated that the ventral pallidum receives enkephalinergic and dopaminergic inputs. The present study evaluated the contribution of dopamine (DA) receptors to opioid-mediated locomotor functions of the ventral pallidum. Using circling behavior as a motor index, it was determined that injection of metabolically stable analogs of enkephalin, directly into the ventral pallidum, produced a dose-dependent, naloxone-antagonizable, increase in the number of rats rotating contralateral to the injected side, as well as the rate at which the animals turned. The frequency of the contralateral rotation, induced by intra-ventral pallidal injection of DADL (which closely mimics the endogenous enkephalin peptides, exhibiting a high affinity for the delta receptor with a moderate affinity for mu receptors), increased with intraperitoneal pretreatment with amphetamine, suggesting that enhanced release of catecholamines potentiated effects of opioids in the ventral pallidum. Systemic pretreatment with the D2-preferring antagonist haloperidol, blocked the effects of DAMGO (a mu-specific agonist) but not those mediated by DADL. In contrast, the D1-specific antagonist SCH 23390 was an effective blocker of responses to both opioid peptides. Further evidence for differential consequences of activating delta or mu opioid receptors was provided by systemic pretreatment with a cholinergic antagonist; atropine attenuated responding to DADL but not to DAMGO. To ascertain if DA receptors within the ventral pallidum were sufficient to influence mu-mediated circling, it was determined that intra-ventral pallidal injection of SCH 23390 or sulpiride (a D2 specific antagonist), at concentrations that did not produce motor effects, attenuated responding to subsequent intra-ventral pallidal injections of DAMGO. Thus, the opioid receptors and DA receptors that modify responses to activation of opioid receptors are both located within the ventral pallidum. These studies point to the critical role of DA in the ventral pallidum in motor behavior induced by stimulation of opioid receptors in the ventral pallidum.