Effects of orphanin FQ on central dopaminergic neuronal activities and prolactin secretion.

Effects of orphanin FQ (OFQ) on central dopaminergic (DA) neurons and serum prolactin (PRL) were examined in ovariectomized, estrogen-primed Sprague-Dawley rats. The activities of central DA neurons, including the tuberoinfundibular (TI), nigrostriatal, mesolimbic, and incertohypothalamic ones, were determined by measuring the levels of 3,4-dihydroxyphenylacetic acid (DOPAC), the major metabolite of dopamine, in their projection regions in the brain by HPLC plus electrochemical detection. Intracerebroventricular administration of OFQ lowered DOPAC levels in the median eminence (ME), striatum, nucleus accumbens, and hypothalamic paraventricular nucleus in a dose (0.01-10 microg)- and time (30-90 min)-dependent manner. In contrast, OFQ increased DOPAC in the suprachiasmatic nucleus and had no effect in the periventricular nucleus. Serum PRL levels exhibited a typical inverse relationship with the activity of TIDA neurons, as determined by DOPAC levels in the ME. In the afternoon, we observed an endogenous decrease of ME DOPAC level accompanied by a PRL surge in estrogen-primed female rats. Although OFQ caused further decrease of ME DOPAC in the afternoon, it failed to augment the PRL surge level. Although pretreatment of an antisense oligodeoxynucleotide against the opioid receptor-like receptor gene had no effect on basal ME DOPAC levels in the morning or afternoon, it attenuated the afternoon PRL surge. Furthermore, it blocked the effects of exogenous OFQ on ME DOPAC and serum PRL levels, whereas the sense or missense oligodeoxynucleotide had no effect. These results indicate that OFQ and its receptors may be involved in the regulation of central DA neuronal activity and PRL secretion.