NEUROPEPTIDE FLFQPQRFAMIDE RECEPTORS WITHIN THE VENTRAL MESENCHEPHALON AND DOPAMINERGIC TERMINAL AREAS - LOCALIZATION AND FUNCTIONAL ANTIOPIOID INVOLVEMENT

The neuropeptide FLFQPQRF amide is a FMRFamide-like peptide with some anti-opiate properties. Neuropeptide FLFQPQRFamide receptors are prese nt in the mammalian central nervous system and have been clearly ident ified as different from opiate receptors. Autoradiography has revealed neuropeptide FLFQPQRFamide receptor localization within the ventral m esencephalon, where opiate receptors are also located. In order to del ineate anatomical localization of neuropeptide FLFQPQRFamide receptors , we used selective chemical lesions of dopaminergic cells and intrins ic perikarya of the ventral mesencephalon, coupled with in vitro autor adiographic techniques. We show that: (i) unilateral lesions of dopami nergic perikarya produced by B-hydroxydopamine did not affect either i psi or contralateral neuropeptide FLFQPQRFamide receptor density withi n the mesencephalon; (ii) unilateral lesions of intrinsic perikarya by ibotenic acid injected into the ventral tegmental area produced a sig nificant reduction of neuropeptide FLFQPQRFamide receptors (40%) in th is region; (iii) in the substantia nigra pars compacta, ibotenic acid unilateral lesions did not affect the density of neuropeptide FLFQPQRF amide receptors; (iv) unilateral 6-hydtoxydopamine or ibotenic acid le sions failed to affect neuropeptide FLFQPQRFamide binding in the dopam inergic projection areas. These results suggest that, like opiate rece ptors, the neuropeptide FLFQPQRFamide binding sites are not localized on dopaminergic neurons but are distributed on both soma of non dopami nergic cells in the Ventral tegmental area and on fibers afferent to t he ventral tegmental area and substantia nigra pars compacta. To avalu ate the possibility that the stimulation of neuropeptide FLFQPQRFamide receptors may affect the opioid modulation of mesocorticolimbic dopam inergic neuron activity, we tested the effects of neuropeptide FLFQPQR Famide ventral tegmental area infusion (0.25-10 mu g) on the behaviora l activation induced by intra-ventral tegmental area morphine infusion . We observed that in the ventral tegmental area, the stimulation of n europeptide FLFQPQRFamide receptors inhibits morphine-induced locomoto r hyperactivity. These results suggest that in the ventral tegmental a rea, neuropeptide FLFQPQRFamide may participate, via an indirect mecha nism, to the control of the mesocorticolimbic dopaminergic system acti vity by counteracting the effect of opioids.