INTRACEREBROVENTRICULAR ORPHANIN FQ NOCICEPTIN SUPPRESSES DOPAMINE RELEASE IN THE NUCLEUS-ACCUMBENS OF ANESTHETIZED RATS

Cloning studies have identified a novel seven transmembrane receptor d isplaying high sequence homology to the three classical opioid recepto rs (mu, delta and kappa).(3,4,7,11,14,17,24,25). This receptor is wide ly distributed throughout the CNS.(1) Recently, an endogenous ligand f or this receptor was isolated (termed either ''orphanin FQ'' or ''noci ceptin'') and identified as a heptadecapeptide showing sequence homolo gy with the endogenous opioids.(13,20) Surprisingly, in contrast to kn own opioids, orphanin FQ displays hyperalgesic rather than analgesic p roperties. Furthermore, in contrast to enkephalins and endorphins, but similarly to dynorphins, this peptide has inhibitory actions upon loc omotor activity.(20) These preliminary data suggest that orphanin FQ s ystems may act in an opposing manner to the previously well-described enkephalin and endorphin systems, Since numerous studies have implicat ed activation of the mesolimbic dopamine pathway to be central to the rewarding actions of opiates such as morphine and heroin, as well as s everal other abused drugs,(6) and also to mediate the hyperlocomotory action of such drugs, we sought to determine the effect of orphanin FQ on this pathway. In accordance with the inhibitory effect of this pep tide on locomotor activity, we now report that orphanin FQ suppresses dopamine release in the nucleus accumbens in a dose-dependent manner, providing the first neurochemical evidence for a modulatory role of th is recently described peptide in the CNS. Copyright (C) 1996 IBRO.