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

Abstract

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.

Lack of involvement of dopamine and serotonin during the orphanin FQ/Nociceptin (OFQ/N)-induced prolactin secretory response

“…Furthermore, they reported inhibition of TIDA neurons at 60 min after OFQ/N administration, a time when prolactin levels had returned to basal values in our study. Therefore, differences between the experimental conditions may account for the discrepancy between our results and those of Shieh and Pan (2001). Our results support the findings of Netti et al (2002), who reported that OFQ/N still stimulated prolactin secretion even when catecholamines were depleted by a-methyl-tyrosine, indicating dopamine inhibition was not necessary for this stimulatory action of OFQ/N.…”

“…Even though our time course was 90 min, OFQ/N still had no effect on the expression of c-fos in the TIDA neurons, confirming the neurochemical results. In contrast, Shieh and Pan (2001) reported a dose and time dependent decrease in DOPAC levels following OFQ/N administration. This effect was observed in the morning, but not in the afternoon, and was prevented by pretreatment with an antisense oligonucleotide against the gene for the OFQ/N receptor.…”

Estradiol Negatively Modulates the Pleiotropic Actions of Orphanin FQ/Nociceptin at Proopiomelanocortin Synapses

“…Indeed, OFQ/N also hyperpolarizes A 12 dopamine and gonadotropin-releasing hormone neurons in the guinea pig ARH [11]. A 12 dopamine neurons tonically inhibit prolactin secretion from the anterior pituitary [69], and so therefore OFQ/N-induced decreases in the neuronal activity of these cells are associated with increases in circulating prolactin concentrations [70]. Given the well-known fact that estradiol increases the excitability of A 12 dopamine neurons [69], it is quite plausible that the decreased ORL1 receptor-mediated signaling observed presently contributes to the activation of these cells.…”

Inhibition of striatal and retinal dopamine release via nociceptin/orphanin FQ receptors

“…An inhibitory effect of N/OFQ on dopamine release has been shown previously in the striatum of the rat (Shieh & Pan, 2001) and the mouse (Schlicker et al ., 1998a) and we show here that such an effect also occurs in the striatum of the guinea‐pig. The maximum extent of inhibition in the guinea‐pig striatum is lower than that obtained in the mouse striatum.…”

“…affects the release of dopamine and this has been shown by direct measurement of transmitter release or electrophysiological techniques for the (i) nigrostriatal (Konya et al ., 1998; Schlicker et al ., 1998a; Shieh & Pan, 2001), (ii) mesolimbic (Murphy et al ., 1996; Murphy & Maidment, 1999; Lutfy et al ., 2001; Shieh & Pan, 2001; Zheng et al ., 2002), (iii) tuberoinfundibular (Wagner et al ., 1998; Shieh & Pan, 2001) and (iv) incertohypothalamic system (Shieh & Pan, 2001). The involvement of NOP receptors in the effect of N/OFQ has so far been proven only in the studies by Shieh & Pan (2001; use of an antisense oligodeoxynucleotide) and by Zheng et al . (2002; use of the weakly potent NOP receptor antagonist [Phe 1 Ψ(CH 2 ‐NH)Gly 2 ]‐N/OFQ(1‐13)NH 2 ).…”