Skip to main content
SpringerLink
Log in

Mesolimbic dopamine neurons: Effects of 6-hydroxydopamine-induced destruction and receptor blockade on drug-induced rotation of rats

  • Original Investigations
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Bilateral injections of 6-hydroxydopamine (6-OHDA) into the nucleus accumbens greatly reduced the dopamine content of this nucleus and the olfactory tubercle and blocked the ipsilateral rotation induced by amphetamine and methamphetamine in rats with unilateral 6-OHDA lesions of the caudate nucleus. In contrast, apomorphine-induced contralateral rotation was enhanced. Similar results were obtained when the destruction of forebrain noradrenergic neurons, normally produced by the nucleus accumbens 6-OHDA lesion, was prevented by desipramine (DMI) pretreatment. Microinjections of the dopamine receptor antagonist haloperidol into the nucleus accumbens did not spread to the olfactory tubercle, as assessed by the distribution of 3H-haloperidol, and blocked circling induced by amphetamine and apomorphine. Amphetamine-induced circling was less effectively blocked by haloperidol injected into the olfactory tubercle. These results suggest that activity at nucleus accumbens dopamine receptors can greatly affect circling behavior, perhaps by amplifying asymmetries of nigrostriatal activity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Breese, G. R., Traylor, T. D.: Depletion of brain noradrenaline and dopamine by 6-hydroxydopamine. Br. J. Pharmacol. 42, 88–99 (1971)

    Google Scholar 

  • Christie, J. E., Crow, T. J.: Turning behaviour as an index of the action of amphetamines and ephedrines on central dopamine-containing neurones. Br. J. Pharmacol. 43, 658–667 (1971)

    Google Scholar 

  • Costall, B., Naylor, R. J.: Neuropharmacological studies on the site and mode of action of ET 495. In: Advances in neurology, vol. 3, D. B. Calne, ed., pp. 281–293. New York: Raven Press 1973

    Google Scholar 

  • Cuello, A. C., Hiley, C. R., Iversen, L. L.: Use of catechol-O-methyltransferase for the enzyme radiochemical assay of dopamine. J. Neurochem. 21, 1337–1340 (1973)

    Google Scholar 

  • Elkhawad, A. O., Woodruff, G. N.: Studies on the behavioural pharmacology of a cyclic analogue of dopamine following its injection into the brains of conscious rats. Br. J. Pharmacol. 54, 107–114 (1975)

    Google Scholar 

  • Farley, I. J., Price, K. S., Hornykiewicz, O.: Dopamine in the limbic regions of the human brain: normal and abnormal. In: Nonstriated dopamine, E. Costa and G. L. Gessa, ed., pp. 57–64. New York: Raven Press 1977

    Google Scholar 

  • Fuxe, K., Corrodi, H., Hökfelt, T., Lidbrink, P., Ungerstedt, U.: Ergocornine and 2-Br-α-ergocryptine. Evidence for prolonged dopamine receptor stimulation. Med. Biol. 52, 121–132 (1974)

    Google Scholar 

  • Fuxe, K., Ungerstedt, U.: Action of caffeine and theophylline on supersensitive dopamine receptors: considerable enhancement of receptor response to treatment with DOPA and dopamine receptor agonists. Med. Biol. 52, 48–54 (1974)

    Google Scholar 

  • Glowinski, J., Iversen, L. L.: Regional studies of catecholamines in the rat brain. J. Neurochem. 13, 655–669 (1966)

    Google Scholar 

  • Green, A. R., Kelly, P. H.: Evidence concerning the involvement of 5-hydroxytryptamine in the locomotor activity produced by amphetamine or tranylcypromine plus L-DOPA. Br. J. Pharmacol. 57, 141–147 (1976)

    Google Scholar 

  • Horn, A. S., Cuello, A. C., Miller, R. J.: Dopamine in the mesolimbic system of the rat brain: endogenous levels and the effects of drugs on the uptake mechanism and stimulation of adenylate cyclase activity. J. Neurochem. 22, 265–270 (1974)

    Google Scholar 

  • Jackson, D. M., Andén, N.-E., Dahlström, A.: A functional effect of dopamine in the nucleus accumbens and in some other dopamine-rich parts of the rat brain. Psychopharmacologia (Berl.) 45, 139–149 (1975)

    Google Scholar 

  • Johnson, A. M., Loew, D. M., Vigouret, J. M.: Stimulant properties of bromocriptine on central dopamine receptors in comparison to apomorphine, (+)-amphetamine and L-DOPA. Br. J. Pharmacol. 56, 59–68 (1976)

    Google Scholar 

  • Kelly, P. H.: Unilateral 6-hydroxydopamine lesions of nigrostriatal or mesolimbic dopamine-containing terminals and the drug-induced rotation of rats. Brain Res. 100, 163–169 (1975)

    Google Scholar 

  • Kelly, P. H.: Drug-induced motor behavior. In: Handbook of psychopharmacology, L. L. Iversen, S. D. Iversen, and S. H. Snyder, eds. New York: Plenum (in press) 1977

    Google Scholar 

  • Kelly, P. H., Iversen, S. D.: Selective 6-OHDA-induced destruction of mesolimbic dopamine neurons: abolition of psychostimulant-induced locomotor activity in rats. Eur. J. Pharmacol. 40, 45–55 (1976)

    Google Scholar 

  • Kelly, P. H., Joyce, E. M., Minneman, K. P., Phillipson, O. T.: Specificity of 6-hydroxydopamine-induced destruction of mesolimbic or nigrostriatal dopamine-containing terminals. Brain Res. 122, 382–387 (1977)

    Google Scholar 

  • Kelly, P. H., Miller, R. J.: The interaction of neuroleptic and muscarinic agents with central dopaminergic systems. Br. J. Pharmacol. 54, 115–121 (1975)

    Google Scholar 

  • Kelly, P. H., Moore, K. E.: Mesolimbic dopaminergic neurones in the rotational model of nigrostriatal function. Nature 263, 695–696 (1976)

    Google Scholar 

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

    Google Scholar 

  • Milson, J. A., Pycock, C. J.: Effects of drugs acting on cerebral 5-hydroxytryptamine mechanisms on dopamine-dependent turning behaviour in mice. Br. J. Pharmacol. 56, 77–85 (1976)

    Google Scholar 

  • Moore, K. E.: Amphetamines-biochemical and behavioral actions in animals. In: Handbook of psychopharmacology, L. L. Iversen, S. D. Iversen, and S. H. Snyder, eds. New York: Plenum (in press) 1977

    Google Scholar 

  • Moore, K. E., Kelly, P. H.: Biochemical pharmacology of mesolimbic and mesocortical dopaminergic neurons. In: Psychopharmacology: a generation of progress. M. A. Lipton, A. DiMascio, and K. F. Killam, ed. New York: Raven Press (in press) 1977

    Google Scholar 

  • Moore, K. E., Phillipson, O. T.: Effects of dexamethasone on phenylethanolamine N-methyltransferase and adrenaline in the brains and superior cervical ganglia of adult and neonatal rats. J. Neurochem. 25, 289–294 (1975)

    Google Scholar 

  • Muller, P., Seeman, P.: Neuroleptics: relation between cataleptic and anti-turning actions, and role of the cholinergic system. J. Pharm. Pharmacol. 26, 981–984 (1974)

    Google Scholar 

  • Pellegrino, L. J., Cushman, A. J.: A stereotaxic atlas of the rat brain. New York: Appleton-Century-Crofts 1968

    Google Scholar 

  • Pijnenburg, A. J. J., Honig, W. M. M., Heyden, J. A. M., van Rossum, J. M.: Effects of chemical stimulation of the mesolimbic dopamine system upon locomotor activity. Eur. J. Pharmacol. 35, 45–58 (1976)

    Google Scholar 

  • Pijnenburg, A. J. J., Honig, W. M. M., van Rossum, J. M.: Inhibition of d-amphetamine induced locomotor activity by injection of haloperidol into the nucleus accumbens of the rat. Psychopharmacologia (Berl.) 41, 87–96 (1975)

    Google Scholar 

  • Pijnenburg, A. J. J., Woodruff, G. N., van Rossum, J. M.: Ergometrine induced locomotor activity following intracerebral injection into the nucleus accumbens. Brain Res. 59, 289–302 (1973)

    Google Scholar 

  • Rech, R. H., Borys, H. K., Moore, K. E.: Alterations in behavior and brain catecholamine levels in rats treated with α-methyl-tyrosine. J. Pharmacol. Exp. Ther. 153, 412–419 (1966)

    Google Scholar 

  • Ungerstedt, U.: Stereotaxic mapping of monoamine pathways in the rat brain. Acta Physiol. Scand. [Suppl.] 367, 1–48 (1971a)

    Google Scholar 

  • Ungerstedt, U.: Striatal dopamine release after amphetamine or nerve degeneration revealed by rotational behaviour. Acta Physiol. Scand. [Suppl.] 367, 49–68 (1971b)

    Google Scholar 

  • Ungerstedt, U.: Postsynaptic supersensitivity after 6-hydroxydopamine induced degeneration of the nigro-striatal dopamine system. Acta Physiol. Scand. [Suppl.] 367, 69–93 (1971c)

    Google Scholar 

  • Ungerstedt, U., Arbuthnott, G. W.: Quantitative recording of rotational behavior in rats after 6-hydroxydopamine lesions of the nigrostriatal dopamine system. Brain Res. 24, 485–493 (1970)

    Google Scholar 

  • Von Voigtlander, P. F., Moore, K. E.: Turning behavior of mice with unilateral 6-hydroxydopamine lesions in the striatum: effects of apomorphine, L-DOPA, amantadine, amphetamine and other psychomotor stimulants. Neuropharmacology 12, 451–462 (1973)

    Google Scholar 

  • Weissman, A., Koe, B. K., Tenen, S. S.: Antiamphetamine effects following inhibition of tyrosine hydroxylase. J. Pharmacol. Exp. Ther. 151, 339–352 (1966)

    Google Scholar 

  • Woodruff, G. N., Kelly, P. H., Elkhawad, A. O.: Effects of dopamine receptor stimulants on locomotor activity of rats with electrolytic or 6-hydroxydopamine-induced lesions of the nucleus accumbens. Psychopharmacology 47, 195–198 (1976)

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, Michigan State University, 48824, East Lansing, Michigan, USA

    P. H. Kelly & K. E. Moore

Authors
  1. P. H. Kelly
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K. E. Moore
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kelly, P.H., Moore, K.E. Mesolimbic dopamine neurons: Effects of 6-hydroxydopamine-induced destruction and receptor blockade on drug-induced rotation of rats. Psychopharmacology 55, 35–41 (1977). https://doi.org/10.1007/BF00432814

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00432814

Key words

Search

Navigation