Skip to main content
Log in

Blockade of nucleus accumbens opiate receptors attenuates intravenous heroin reward in the rat

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

Abstract

A quaternary derivative of naloxone, methyl naloxonium chloride (MN), was administered intracerebrally to rats trained to self-administer heroin intravenously. Increases in intravenous (IV) heroin self-administration rates were found following injections of low doses of MN into the nucleus accumbens (N.Acc), but not following injections of low doses of MN into the ventral tegmental area (VTA). These results were interpreted to suggest that the rewarding properties of IV heroin were decreased following N.Acc opiate receptor blockade. The relative insensitivity of the VTA to MN treatment was taken to suggest that VTA opiate receptors are either not essential or play a secondary role in mediating IV heroin self-administration. The present data support the notion that post-synaptic N.Acc opiate receptors play a crucial role in maintaining IV heroin self-administration.

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

Access this article

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

  • Bianchi G, Fiocchi R, Tavani A, Manara L (1982) Quaternary narcotic antagonists relative ability to prevent antinociception and gastrointestinal transit inhibition in morphine-treated rats as an index of peripheral selectivity. Life Sci 30:1875–1883

    Google Scholar 

  • Bozarth MA, Wise RA (1981) Intracranial self-administration of morphine into the ventral tegmental area in rats. Life Sci 28:551–555

    Google Scholar 

  • Bozarth MA, Wise RA (1983) Neural substrates of opiate reinforcement. Prog Neuropsychopharmacol Biol Psychiatry 7:569–575

    Google Scholar 

  • Britt MD, Wise RA (1983) Ventral tegmental site of opiate reward: antagonism by a hydrophilic opiate receptor blocker. Brain Res 258:105–108

    Google Scholar 

  • Ettenberg A, Pettit HO, Bloom FE, Koob GF (1982) Heroin and cocaine intravenous self-administration in rats: Mediation by separate neural systems. Psychopharmacology 78:204–209

    Google Scholar 

  • Fink JS, Smith GP (1980) Mesolimbocortical dopamine terminal fields are necessary for normal locomotor and investigatory exploration in rats. Brain Res 199:359–385

    Google Scholar 

  • Glick SD, Cox RS, Crane AM (1975) Changes in morphine self-administration and morphine dependence after lesions of the caudate nukleus in rats. Psychopharmacologia 41:219–224

    Google Scholar 

  • Goeders NE, Lane TD, Smith JE (1984) Self-administration of methionine enkephalin into the nucleus accumbens. Pharmacol Biochem Behav 20:451–455

    Google Scholar 

  • Goldberg SR, Woods JH, Schuster CR (1971) Nalorphine-induced changes in morphine self-administration in rhesus monkeys. J Pharmacol Exp Ther 176:464–471

    Google Scholar 

  • Kalivas PW, Widerlov E, Stanley D, Breese G, Prange AJ Jr (1983) Enkephalin action on the mesolimbic system: a dopamine-dependent and dopamine-independent increase in locomotor activity. J Pharmacol Exp Ther 227(1):1–9

    Google Scholar 

  • Kelley AE, Stinus L, Iversen SD (1980) Interactions between d-Ala-Met-enkephalin, A10 dopaminergic neurons, and spontaneous behavior in the rat. Behav Brain Res 1:3–24

    Google Scholar 

  • Koob GF, Bloom FE (1983) Behavioral effects of opioid peptides. Br Med J 39(1):89–94

    Google Scholar 

  • Koob GF, Pettit HO, Ettenberg A, Bloom FE (1984) Effects of opiate antagonists and their quaternary derivatives on heroin self-administration in the rat. J Pharmacol Exp Ther 229(2):481–486

    Google Scholar 

  • Kosterlitz HW, Waterfield AA, Berthoud V (1974) Report to the 36th Annual Scientific Meeting. Committee on Drug Dependence. pp 56–65

  • Olds ME (1982) Reinforcing effects of morphine in the nucleus accumbens. Brain Res 237:429–440

    Google Scholar 

  • Pellegrino LJ, Pellegrino AS, Cushman AJ (1979) A stereotaxic atlas of the rat brain. Plenum Press New York

    Google Scholar 

  • Pert A, Sivit C (1977) Neuroanatomical focus for morphine and enkephalin-induced hypermotility. Nature 265:645–647

    Google Scholar 

  • Pert CB, Pert A, Chang JK, Fong BTW (1976) (D-Ala2)-Metenkephalinamide: A potent, long-lasting synthetic pentapeptide analgesic. Science 194:330–332

    Google Scholar 

  • Pettit HO, Ettenberg A, Bloom FE, Koob GF (1984) Destruction of dopamine in the nucleus accumbens selectively attenuates cocaine but not heroin self-administration in rats. Psychopharmacology 84:167–173

    Google Scholar 

  • Pickens R, Meisch RA, Thompson T (1978) Drug self-administration: An analysis of the reinforcing effects of drugs. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of Psychopharmacology, vol 12, Plenum Press New York, pp 1–37

    Google Scholar 

  • Roberts DCS, Corcoran ME, Fibiger HC (1977) On the role of ascending catecholamine systems in intravenous self-administration of cocaine. Pharmacol Biochem Behav 6:615–620

    Google Scholar 

  • Roberts DCS, Koob GF, Klonoff P, Fibiger HC (1980) Extinction and recovery of cocaine self-administration following 6-hydroxydopamine lesions of the nucleus accumbens. Pharmacol Biochem Behav 12:781–787

    Google Scholar 

  • Russell J, Bass P, Goldberg LI, Schuster CR, Merz H (1982) Antagonism of gut, but not central effects of morphine with quaternary narcotic antagonists. Eur J Pharmacol 78:255–261

    Google Scholar 

  • Stinus L, Koob GF, Ling N, Bloom FE, LeMoal M (1980) Locomotor activation induced by infusion of endorphins into the ventral tegmental area: evidence for opiate-dopamine interactions. Proc Natl Acad Sci USA 97:2323–2327

    Google Scholar 

  • Vaccarino FJ, Franklin KBJ (1982) Self-stimulation and circling reveal functional differences between the medial and lateral substantia nigra. Behav Brain Res 5:281–295

    Google Scholar 

  • Vaccarino FJ, Pettit HO, Bloom FE, Koob GF (1985) Effects of intra-cerebroventricular administration of methyl naloxonium chloride on heroin self-administration in the rat. Pharmacol Biochem Behav (in press)

  • Valentino RJ, Katz JL, Medihradsky F, Woods JM (1983) Receptor binding, antagonist, and withdrawal precipitating properties of opiate antagonists. Life Sci 32:2887–2896

    Google Scholar 

  • Weeks JR, Collins RJ (1976) Changes in morphine self-administration in rats induced by prostaglandin E and naloxone. Prostaglandins 12:11–19

    Google Scholar 

  • Wilson MC, Schuster CR (1972) The effects of chlorpromazine on psychomotor stimulant self-administration in the rhesus monkey. Psychopharmacologia 26:115–126

    Google Scholar 

  • Yokel RA, Wise RA (1975) Increased lever pressing for anphetamine after pimozide in rats: implications for a dopamine theory of reward. Science 187:547–549

    Google Scholar 

  • Yokel RA, Wise RA (1976) Attenuation of intravenous amphetamine reinforcement by central dopamine blockade in rats. Psychopharmacologia 48:311–318

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vaccarino, F.J., Bloom, F.E. & Koob, G.F. Blockade of nucleus accumbens opiate receptors attenuates intravenous heroin reward in the rat. Psychopharmacology 86, 37–42 (1985). https://doi.org/10.1007/BF00431681

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00431681

Key words

Navigation