Summary
Opiates and opioid peptides are known to influence the dopaminergic (DA) neurons in the midbrain. The purpose of this study was to map and quantify the density of kappa and delta opioid receptor subtypes in the retrorubral field, substantia nigra, and ventral tegmental area and related nuclei, which contain DA nuclei A8, A9, and A10, respectively. Sections through the rostral-caudal extent of the rat midbrain were stained with an antibody against tyrosine hydroxylase, as a DA cell marker, and comparable sections were processed for in vitro receptor autoradiography using the kappa-selective ligand, U-69593, and the delta-selective ligand, D-Pen2, D-Pen5-enkephalin. In general, both kappa and delta ligands exhibited low levels of specific binding in regions occupied by the midbrain DA neurons.Kappa binding (4–8 fmol/mg tissue) was high throughout the rostral-caudal extent of the substantia nigra, in rostral portions of the ventral tegmental area, and in the nucleus paranigralis; low binding occurred in the retrorubral field and central linear nucleus raphe.Delta binding (6–18 fmol/mg tissue) was high in the caudal portion of the substantia nigra pars reticulata, and in the medial terminal nucleus of the accessory optic system (a region previously shown to contain DA dendrites). The kappa and delta receptor binding is heterogeneously distributed in regions occupied by midbrain dopaminergic neurons, and several fold lower than the binding of mu opioid receptors in the same brain regions.
Similar content being viewed by others
References
Dahlström A, Fuxe K (1964) Evidence for the existence of monoamine-containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons. Acta Physiol Scand 62 [Suppl 232]: 1–55
DiChiara G, Imperato A (1988a) Opposite effects of mu and kappa opiate agonists on dopamine release in the nucleus accumbens and in the dorsal caudate of freely moving rats. J Pharmacol Exp Ther 224: 1067–1080
DiChiara G, Imperato A (1988b) Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolombic system of freely moving rats. Proc Natl Acad Sci 85: 5274–5278
Dilts RP, Kalivas PW (1989) Autoradiographic localization of μ-opioid and neurotensin receptors within the mesolimbic dopamine system. Brain Res 488: 311–327
Dilts RP, Kalivas PW (1990) Autoradiographic localization of delta opioid receptors within mesocorticolimbic dopamine system using125I-DPDPE. Synapse 6: 121–132
Eghbali M, Santoro C, Paredes W, Gardner EL, Zukin RS (1987) Visualization of multiple opioid-receptor types in rat striatum after specific mesencephalic lesions. Proc Natl Acad Sci 84: 6582–6587
Fallon JH, Moore RY (1978) Catecholamine innervation of the basal forebrain. IV. Topography of the dopamine projection to the basal forebrain and neostriatum. J Comp Neurol 180: 545–580
German DC, Manaye KF (1993) Midbrain dopaminergic neurons (nuclei A8, A9 and A10): 3-dimensional reconstruction in rat. J Comp Neurol (in press)
German DC, Dubach M, Askari S, Speciale SG, Bowden DM (1988) 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian syndrome inMacaco, fascicularis: which midbrain dopaminergic neurons are lost? Neuroscience 24: 161–174
German DC, Speciale SG, Manaye KF, Sadeq M (1992) Opioid receptors in midbrain dopaminergic regions of the rat. I. Mu receptor autoradiography. J Neural Transm 91: 39–52
Giolli RA, Blanks RHI, Torigoe Y (1984a) Pretectal and brain stem projections of the medial terminal nucleus of the accessory optic system of the rabbit and rat as studied by anterograde and retrograde neuronal tracing methods. J Comp Neurol 227: 228–251
Giolli RA, Schmued LC, Fallon JH (1984b) A retinomesotelencephalic pathway in the rat. Neurosci Lett 53: 1–7
Giolli RA, Blanks RHI, Torigoe Y, Williams DD (1985) Projections of medial terminal accessory optic nucleus, ventral tegmental nuclei, and substantia nigra of rabbit and rat as studied by retrograde axonal transport of horseradish peroxidase. J Comp Neurol 232: 99–116
Johnson SW, North RA (1992) Opioids excite dopamine neurons by hyperpolarization of local interneurons. J Neurosci 12: 483–488
Lacey MG, Mercuri NB, North RA (1989) Two cell types in rat substantia nigra zona compacta distinguished by membrane properties and the actions of dopamine and opioids. J Neurosci 9: 1233–1241
Lavin A, Garcia-Munoz M (1985) Electrophysiological changes in substantia nigra after dynorphin administration. Brain Res 369: 298–302
Liang C-L, Kozlowski GP, German DC (1992a) Leucine5-enkephalin afferents to midbrain dopaminergic neurons: light and electron microscopic examination. J Comp Neurol (in press)
Liang C-L, Kozlowski GP, Joseph SA, German DC (1992b) ACTH1–39 input to mesocorticolimbic dopaminergic neurons: light and electron microscopic examination. Neurosci Lett (in press)
Mansour A, Lewis ME, Khachaturian H, Akil H, Watson SJ (1986) Pharmacological and anatomical evidence of selective μ, δ and κ opioid receptor binding in rat brain. Brain Res 399: 69–79
Mansour A, Khachaturian H, Lewis ME, Akil H, Watson SJ (1987) Autoradiographic differentiation of μ, delta and kappa opioid receptors in the rat forebrain and midbrain. J Neurosci 7: 2445–2464
McLean S, Rothman RD, Herkenham M (1986) Autoradiographic localization of u- and δ-receptors in the forebrain of the rat. Brain Res 378: 49–60
Moskowitz AS, Goodman RR (1984) Light microscopic autoradiographic localization of μ and delta opioid binding sites in the mouse central nervous system. J Neurosci 4: 1331–1342
Mucha RF, Herz A (1985) Motivational properties of kappa and mu-opioid receptor agonists studied with place and taste preference conditioning procedures. Psychopharmacology 86: 274–280
Nock B, Rajpara A, O'Connor LH, Cicero TH (1988) Autoradiography of [3H]U-69593 binding sites in rat brain: evidence for K opioid receptor subtypes. Eur J Pharmacol 154: 27–34
Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates, 2nd ed. Academic Press, Orlando FL
Pickel VM, Chan J, Sesack SR (1991) Monosynaptic input to dopaminergic neurons in rat substantia nigra and ventral tegmental area from dynorphin-immunoreactive terminals. Neurosci Abstr 17: 718
Sesack SR, Pickel VM (1992) Dual ultrastructural localization of enkephalin and tyrosine hydroxylase immunoreactivity in the rat ventral tegmental area: multiple substrates for opiate-dopamine interactions. J Neurosci 12: 1335–1350
Shippenberg TS, Bals-Kubik R, Herz A (1987) Motivational properties of opioid: evidence that an activation of delta receptors mediates reinforcement processes. Brain Res 436: 234–239
Tempel A, Zukin RS (1987) Neuroanatomical patterns of μ, δ, and K opioid receptors of rat brain as determined by quantitative in vitro autoradiography. Proc Natl Acad Sci 84: 4308–4312
Thompson LA, Walker JM (1987) Inhibitory effects of the K opiate U 50,488 in the substantia nigra pars reticulata. Brain Res 517: 81–87
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Speciale, S.G., Manaye, K.F., Sadeq, M. et al. Opioid receptors in midbrain dopaminergic regions of the rat II. Kappa and delta receptor autoradiography. J. Neural Transmission 91, 53–66 (1993). https://doi.org/10.1007/BF01244918
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01244918