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Anatomical analysis of the involvement of mesolimbocortical dopamine in the locomotor stimulant actions ofd-amphetamine and apomorphine

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Abstract

Lesion studies employing 6-hydroxydopamine (6-OHDA) suggest that locomotor hyperactivity induced by certain stimulant drugs is dependent on dopaminergic neurotransmission in the nucleus accumbens (NACC). However, studies to date have not adequately controlled for the reported effects of 6-OHDA on baseline (non-drug) activity and on DA levels in other terminal regions. Slow bilateral infusions of 6-OHDA into the NACC, but not into olfactory tubercle (OT) or medial prefrontal cortex (mPFCx), reducedd-amphetamine (0.5 mg/kg SC) hyperactivity and resulted in a “supersensitive” (hyperactive) response to a low dose of apomorphine (0.1 mg/kg SC) in photocell cages. Direct observation revealed no behavioral changes in OT lesioned rats challenged with apomorphine which might correspond to a “denervation supersensitivity” syndrome. Assays of DA and 5-hydroxytryptamine (5-HT) in mPFCx, OT, NACC, and caudate-putamen revealed that 6-OHDA infusion into NACC caused substantial DA loss in NACC, OT and mPFCx, whereas infusion at mPFCx or OT sites depleted DA locally (>85% loss) with little or no remote change. Concentrations of 5-HT were little altered by 6-OHDA, except for a local depletion in mPFCx. The present results confirm the importance of nucleus accumbens DA in the expression of locomotor stimulation induced by apomorphine andd-amphetamine, and suggest that the mPFCx and OT do not make an important contribution.

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References

  • Carter CJ, Pycock CJ (1980) Behavioural and biochemical effects of dopamine and noradrenaline depletion within the medial prefrontal cortex of the rat. Brain Res 192:163–176

    PubMed  Google Scholar 

  • Clarke PBS, Kumar R (1983) The effects of nicotine on locomotor activity in non-tolerant and tolerant rats. Br J Pharmacol 78:329–337

    PubMed  Google Scholar 

  • Clarke PBS, Fu DW, Jakubovic A, Fibiger NC (1988) Evidence that mesolimbic dopaminergic activation underlies the locomotor stimulant action of nicotine in rats. J Pharmacol Exp Ther 246:701–708

    PubMed  Google Scholar 

  • Cools AR (1986) Mesolimbic dopamine and its control of locomotor activity in rats: differences in pharmacology and light/dark periodicity between the olfactory tubercle and the nucleus accumbens. Psychopharmacology 88:451–459

    PubMed  Google Scholar 

  • Costall B, Marsden CD, Naylor RJ, Pycock CJ (1977) Stereotyped behaviour patterns and hyperactivity induced by amphetamine and apomorphine after discrete 6-hydroxydopamine lesions of extrapyramidal and mesolimbic nuclei. Brain Res 123:89–111

    PubMed  Google Scholar 

  • Fink JS, Smith GP (1979) Abnormal pattern of amphetamine locomotion after 6-hydroxydopamine lesion of the anteromedial caudate. Pharmacol Biochem Behav 11:23–30

    Google Scholar 

  • Jonsson G (1983) Chemical lesioning techniques: monoamine neurotoxins. In: Bjorklund A, Hokfelt T (eds) Handbook of chemical neuroanatomy. Elsevier, Amsterdam, pp 463–507

    Google Scholar 

  • Joyce EM, Koob GF (1981) Amphetamine-, scopolamine-, and caffeine-induced locomotor activity following 6-hydroxydopamine lesions of the mesolimbic dopamine system. Psychopharmacology 73:311–313

    PubMed  Google Scholar 

  • Joyce EM, Stinus L, Iversen SD (1983) Effect of injections of 6-OHDA into either nucleus accumbens septi or frontal cortex on spontaneous and drug-induced activity. Neuropharmacology 22:1141–1145

    PubMed  Google Scholar 

  • Kafetzopoulos E (1986) Effects of amphetamine and apomorphine on locomotor activity after kainic acid lesion of the nucleus accumbens septi in the rat. Psychopharmacology 88:271–274

    PubMed  Google Scholar 

  • Kelly PH, Iversen SD (1976) Selective 6-OHDA-induced destruction of mesolimbic dopamine neurons: abolition of psychostimulant-induced locomotor activity in rats. Eur J Pharmacol 40:45–56

    PubMed  Google Scholar 

  • Kelly PH, Roberts DCS (1983) Effects of amphetamine and apomorphine on locomotor activity after 6-OHDA and electrolytic lesions of the nucleus accumbens septi. Pharmacol Biochem Behav 19:137–143

    PubMed  Google Scholar 

  • Kelly PH, Seviour PW, Iversen SD (1975) Amphetamine and apomorphine responses in the rat following 6-OHDA lesions of the nucleus accumbens septi and corpus striatum. Brain Res 94:507–522

    PubMed  Google Scholar 

  • Koob GF, Riley SJ, Smith SC, Robbins TW (1978) Effects of 6-hydroxydopamine lesions of the nucleus accumbens septi and olfactory tubercle on feeding, locomotor activity, and amphetamine anorexia in the rat. J Comp Physiol Psychol 92:917–927

    PubMed  Google Scholar 

  • Koob GF, Stinus L, Le Moal ML (1981) Hyperactivity and hypoactivity produced by lesions to the mesolimbic dopamine system. Behav Brain Res 3:341–359

    PubMed  Google Scholar 

  • Kubos LK, Moran TH, Robinson RG (1987) Differential and asymmetrical behavioral effects of electrolytic or 6-hydroxydopamine lesions of the nucleus accumbens. Brain Res 401:147–151

    PubMed  Google Scholar 

  • Makanjuola ROA, Ashcroft GW (1982) Behavioural effects of electrolytic and 6-hydroxydopamine lesions of the accumbens and caudate-putamen nuclei. Psychopharmacology 76:333–340

    Google Scholar 

  • Makanjuola ROA, Dow RC, Ashcroft GW (1980) Behavioural responses to stereotactically controlled injections of monoamine neurotransmitters into the accumbens and caudate-putamen nuclei. Psychopharmacology 71:227–235

    PubMed  Google Scholar 

  • Martin-Iversin MT, Szostak C, Fibiger HC (1986) 6-Hydroxydopamine lesions of the medial prefrontal cortex fail to influence intravenous self-administration of cocaine. Psychopharmacology 88:310–314

    Google Scholar 

  • Paxinos W, Watson C (1982) The rat brain in stereotaxic coordinates. Academic Press, New York

    Google Scholar 

  • Pijnenburg AJJ, Honig WMM, van Rossum JM (1975) Inhibition ofd-amphetamine-induced locomotor activity by injection of haloperidol into the nucleus accumbens of the rat. Psychopharmacology 41:87–95

    Google Scholar 

  • Pijnenburg AJJ, Honig WMM, van der Heyden JAM, van Rossum JM (1976) Effects of chemical stimulation of the mesolimbic dopamine system upon locomotor activity. Eur J Pharmacol 35:45–58

    PubMed  Google Scholar 

  • Pycock CJ, Carter CJ, Kerwin RW (1980) Effect of 6-hydroxydopamine lesions of the medial prefrontal cortex on neurotransmitter systems in subcortical sites in the rat. J Neurochem 43:91–99

    Google Scholar 

  • Robbins TW, Roberts DCS, Koob GF (1983) Effects ofd-amphetamine and apomorphine upon operant behavior and schedule-induced licking in rats with 6-hydroxyxdopamine-induced lesions of the nucleus accumbens. J Pharmacol Exp Ther 224:662–673

    PubMed  Google Scholar 

  • Robinson RG, Stitt TG (1981) Intracortical 6-hydroxydopamine induces an asymmetric behavioral response in the rat. Brain Res 213:387–395

    PubMed  Google Scholar 

  • Schultz W (1982) Depletion of dopamine in the striatum as an experimental model of Parkinsonism: direct effects and adaptive mechanisms. Prog Neurobiol 18:121–166

    PubMed  Google Scholar 

  • Swerdlow NR, Vaccarino FJ, Amalric M, Koob GF (1986) The neural substrates for the motor-activating properties of psychostimulants: a review of recent findings. Pharmacol Biochem Behav 25:233–248

    PubMed  Google Scholar 

  • Taghoutzi K, Simon H, Louilot A, Herman JP, Le Moal M (1985) Behavioral study after local injection of 6-hydroxydopamine into the nucleus accumbens in the rat. Brain Res 344:9–20

    PubMed  Google Scholar 

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Clarke, P.B.S., Jakubovic, A. & Fibiger, H.C. Anatomical analysis of the involvement of mesolimbocortical dopamine in the locomotor stimulant actions ofd-amphetamine and apomorphine. Psychopharmacology 96, 511–520 (1988). https://doi.org/10.1007/BF02180033

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  • DOI: https://doi.org/10.1007/BF02180033

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