Summary
The possible role of the nucleus accumbens (ACB) and, in some experiments, the septum mediale (SM) in mediating alterations in locomotor activity, produced by various opioids, was evaluated in the rat, the drug being injected either into the left central part of the ACB or into the left SM. Morphine, predominantly acting at the mu-type receptors, given in larger doses (13 or 40 nmol into the ACB) produced depression of locomotor activity and catalepsy, whereas 2.5 nmol were ineffective. Co-administration of naloxone into the ACB suppressed the effects of morphine.d-ala2,d-leu5-enkephalin (DADL), a preferential delta-type receptor agonist, produced a biphasic effect on locomotor activity, namely an inhibition of it and a catalepsy, followed by a locomotor activation. This effect was observed after 4 or 13 nmol; 1 nmol produced a delayed locomotor activation without any previous inhibition, whereas 0.4 or 0.1 nmol were ineffective. Equimolar doses of naloxone, when coadministered with DADL, only partially antagonized these effects of DADL. In contrast, co-administration of a small dose of DADL and an excess dose of naloxone into the ACB produced an immediate increase in locomotor activity. Injections of a predominant kappa type receptor agonist, MR 2033-Cl, were ineffective.
Injection of DADL, either alone or combined with naloxone into the SM (1 nmol) produced an immediate stimulation of locomotor activity.
The results suggest that locomotor depression and catalepsy may be mediated by opioid receptors of the mutype in the ACB, whereas locomotor stimulation is due to an action on delta type receptors, an effect which may be masked by simultaneous stimulation of mu-type receptors under certain conditions. Kappa-type receptors apparently are not involved in any of these effects. In addition, a diffusion of DADL to the adjacent SM may contribute to locomotor stimulation.
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References
Andén NE, Johnels B (1977) Effect of local application of apomorphine to the corpus striatum and to the nucleus accumbens on the reserpine-induced rigidity in rats. Brain Res 133:386–389
Broekkamp CLE, Phillips AG, Cools AR (1979) Stimulant effects of enkephalin micro-injection into the dopaminergic A10 area. Nature 278:560–562
Carey RJ (1982) Septal lesions enhance hyperactivity induced either by amphetamine or leseions of the nucleus accumbens septi. Behav Brain Res 5:43–52
Costall B, Naylor RJ (1974) On catalepsy and catatonia and the predictability of the catalepsy test for neuroleptic activity. Psychopharmacologia 34:233–241
Costall B, Fortune DH, Naylor RJ (1978) The induction of catalepsy and hyperactivity by morphine administered directly into the nucleus accumbens of rats. Eur J Pharmacol 49:49–64
Di Chiara G, Vargiu L, Porceddu ML, Longoni R, Mulas A, Gessa GL (1977) Indirect activation of the Da system as a possible mechanism for the stimulatory effects of narcotic analgesics. In: Costa E, Gessa GL (eds) Advances in biochemical psychopharmacology, vol 16. Raven Press, New York, pp 571–575
Fifková E, Maršala J (1967) Stereotaxic atlases for the cat, rabbit and rat. In: Bureš J, Petrán M, Zachar J (eds) Electrophysiological methods in biological research. Academic Press, New York, pp 653–731
Gillan MGC, Kosterlitz HW, Paterson SJ (1980) Comparison of the binding characteristics of tritiated opiates and opioid peptides. Br J Pharmacol 70:481–490
Goodman RR, Snyder SH (1982) κ-Opiate receptors localized by autoradiography to deep layers of cerebral cortex: relation to sedative effects. Proc Natl Acad Sci USA 79:5703–5707
Goodman RR, Snyder SH, Kuhar MJ, Young WS, III (1980) Differentiation of delta and mu opiate receptor localizations by light microscopic autoradiography. Proc Natl Acad Sci USA 77:6239–6243
Havemann U, Kuschinsky K (1982) Neurochemical aspects of the opioid-induced ‘catatonia’. Neurochem Int 4: 199–215
Havemann U, Winkler M, Kuschinsky K (1983) The effects ofd-ala2,d-leu5-enkephalin injections into the nucleus accumbens on the motility of rats. Life Sci 33 Suppl I: 627–630
Jacquet YF, Lajtha A (1973) Morphine action at central nervous system sites in rat: analgesia or hyperalgesia depending on site and dose. Science 182:490–492
Jones DL, Mogenson GJ, Wu M (1981) Injections of dopaminergic, cholinergic, serotoninergic and GABAergic drugs into the nucleus accumbens: effects on locomotor activity in the rat. Neuropharmacology 20:29–37
Joyce EM, Iversen SD (1979) The effect of morphine applied locally to mesencephalic cell bodies on spontaneous motor activity in the rat. Neurosci Lett 14:207–212
Joyce EM, Koob GF, Strecker R, Iversen SD, Bloom FE (1981) The behavioural effects of enkephalin analogues injected into the ventral tegmental area of globus pallidus. Brain Res 221:359–370
Kalivas PW, Widerlöw E, Stanley D, Breese G, Prange AJ Jr (1983) Enkephalin action on the mesolimbic system: a dopamine-dependent and a dopamin-independent increase in locomotor activity. J Pharmacol Exp Ther 227:229–237
König JFR, Klippel RA (1963) The rat brain. A stereotaxic atlas of the forebrain and lower parts of the brain stem. Williams and Wilkins Co, Baltimore
Kosterlitz HW, Paterson SJ (1980) Characterization of opioid receptors in nervous tissue. Proc Roy Soc (Lond) B 210:113–122
Kuschinsky K, Hornykiewicz O (1972) Morphine catalepsy in the rat: relation to striatal dopamine metabolism. Eur J Pharmacol 19:119–122
Le Bars D, Guilbaud G, Jurna I, Besson JM (1976) Differential effects of morphine on responses of dorsal horn lamina V type cells elicited by A and C fibre stimulation in the spinal cat. Brain Res 115:518–524
Lomax P (1966) The distribution of morphine following intracerebral microinjection. Experientia 22:249–250
Moleman P, van Valkenburg CFM, v d Kroght JA (1984) Effects of morphine on dopamine metabolism in rat striatum and limbic structures in relation to the activity of dopaminergic neurones. Naunyn-Schmiedeberg's Arch Pharmacol 327:208–213
Pert A, Sivit C (1977) Neuroanatomical focus for morphine and enkephalin-induced hypermotility. Nature 265:645–647
Pollard H, Llorens C, Bonnet JJ, Costentin J, Schwartz JC (1978) Opiate receptors on mesolimbic dopaminergic neurons. Neurosci Lett 7:295–299
Stinus GF, Knoob GF, Ling N, Bloom FE, Le Moal M (1980) Locomotor activation induced by infusion of endorphins into the ventral tegmental area: evidence for opiate-dopamine interactions. Proc Natl Acad Sci USA 77:2323–2327
Tseng LF, Wei ET, Loh HH, Hao Li C (1980) β-Endorphin: central sites of analgesia, catalepsy and body temperature changes in rats. J Pharmacol Exp Ther 214:328–332
Westerink BHC, Korf J (1976) Regional rat brain levels of 3,4-dihydrophenylacetic acid and homovanillic acid: concurrent fluorometric measurement and influence of drugs. Eur J Pharmacol 38:281–291
Winkler M, Havemann U, Kuschinsky K (1982) Unilateral injection of morphine into the nucleus accumbens induces akinesia and catalepsy but no spontaneous muscular rigidity in rats. Naunyn-Schmiedeberg's Arch Pharmacol 318:143–147
Yim CY, Mogenson GJ (1982) Response of nucleus accumbens to amygdala stimulation and its modification by dopamine. Brain Res 239:401–415
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Havemann, U., Kuschinsky, K. Locomotor activity of rats after injection of various opiods into the nucleus accumbens and the septum mediale. Naunyn-Schmiedeberg's Arch. Pharmacol. 331, 175–180 (1985). https://doi.org/10.1007/BF00634235
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DOI: https://doi.org/10.1007/BF00634235