Nucleus accumbens as a substrate for the aversive stimulus effects of opiate withdrawal (original) (raw)

Abstract

Previous studies from our laboratory using methylnaloxonium, a hydrophilic antagonist, showed that opiate receptors in the region of the nucleus accumbens are important for the acute reinforcing effects of heroin in non-dependent rats. A similar increased sensitivity to the response disruptive effects of intracerebrally injected methylnaloxonium in opiate dependent rats was observed in a fixed-ratio (FR) baseline of operant behaviors. These results suggest that the same opiate receptors in the region of the nucleus accumbens important for the positive reinforcing stimulus properties of opiates may also be responsible for the response disruptive, aversive stimulus properties of opiate withdrawal. These results also suggest that the neural substrates of some aspects of dependence may be partly related to those of the reinforcing effects of opiates. In particular, it is hypothesized that “euphoria” and “dysphoria” induced by opiates may reflect opponent motivational processes operating at a cellular level within the nucleus accumbens.

Access this article

Log in via an institution

Subscribe and save

• Get 10 units per month
• Download Article/Chapter or eBook
• 1 Unit = 1 Article or 1 Chapter
• Cancel anytime Subscribe now

Buy Now

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

Instant access to the full article PDF.

Similar content being viewed by others

References

• Adler MW, Geller EB, Beeton PB, Gildenberg PL (1978) Inability of acute or chronic thalamic, limbic, or cortical lesions to alter narcotic dependence and abstinence in rats. Dev Neurosci 4:51–52
  Google Scholar
• Bozarth MA, Wise RA (1984) Anatomically distinct opiate receptor fields mediate reward and physical dependence. Science 224:516–517
  Google Scholar
• Charney DS, Heninger GR, Kleber HD (1986) The combined use of clonidine and naltrexone as a rapid, safe, and effective treatment of abrupt withdrawal from methadone. Am J Psychiatry 143:831–837
  Google Scholar
• Geller I, Seifter J (1960) The effect of meprobamate, barbiturates, _d_-amphetamine and promazine on experimentally-induced conflict in the rat. psychopharmacologia 1:482–491
  Google Scholar
• Gellert VF, Sparber SB (1977) A comparison of the effects of naloxone upon body weight loss and suppression of fixed-ratio operant behavior in morphine dependent rats. J Pharmacol Exp Ther 201:44–54
  Google Scholar
• Gray JA (1977) Drug effects on fear and frustration: possible limbic site of action of minor tranquillisers. In: Iversen LL, Iverson SD, Snyder SM (eds) Handbook of psychopharmacology, vol 8. Plenum Press, New York, pp 433–530
  Google Scholar
• Jaffe JH (1987) Drug addiction and drug abuse. In: Gilman AG, Goodman LS, Rall TW (eds) Goodman and Gilman's The pharmacological basis of therapeutics. MacMillan, New York, pp 532–580
  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 229:481–486
  Google Scholar
• Pellegrino LJ, Pellegrino AS, Cushman AJ (1979) A stereotaxic atlas of the rat brain. Plenum Press, New York
  Google Scholar
• Sahakian BJ, Koob GF (1978) The relationship between pipradrol-induced responding for electrical brain stimulation, stereotyped behavior and locomotor activity. Neuropharmacology 17:363–366
  Google Scholar
• Sparber SB, Meyer DR (1978) Clonidine antogonizes naloxone induced suppression of conditioned behavior and bodyweight loss in morphine dependent rats. Pharmacol Biochem Behav 9:319–325
  Google Scholar
• Vaccarino FJ, Bloom FE, Koob GF (1985a) Blockade of nucleus accumbens opiate receptors attenuates intravenous heroin reward in the rat. Psychopharmacology 85:37–42
  Google Scholar
• Vaccarino FJ, Pettit HO, Bloom FE, Koob GF (1985b) Effects of intracerebroventricular administration of methylnaloxonium chloride on heroin self-administration in the rat. Pharmacol Biochem Behav 23:495–498
  Google Scholar
• Way EL, Loh HH, Shen FH (1969) Simultaneous quantitative assessment of morphine tolerance and physical dependence. J Pharmacol Exp Ther 167:1–8
  Google Scholar
• Wei E, Loh HH, Way EL (1972) Neuroanatomical correlates of morphine dependence. Science 177:616–617
  Google Scholar
• Wei E, Loh HH, Way EL (1973) Brain sites of precipitated abstinence in morphine-dependent rats. J Pharmacol Exp Ther 185:108–115
  Google Scholar
• Yoburn BC, Chen J, Huang T, Inturrsi CE (1985) Pharmacokinetics and pharmacodynamics of subcutaneous morphine pellets in the rat. J Pharmacol Exp Ther 235:282–286
  Google Scholar

Download references

Author information

Authors and Affiliations

1. Department of Basic and Clinical Research, Research Institute of Scripps Clinic, 10666 North Torrey Pines Road, 92037, La Jolla, CA, USA
   G. F. Koob, T. L. Wall & F. E. Bloom

Authors

1. G. F. Koob
   You can also search for this author inPubMed Google Scholar
2. T. L. Wall
   You can also search for this author inPubMed Google Scholar
3. F. E. Bloom
   You can also search for this author inPubMed Google Scholar

Rights and permissions

About this article

Cite this article

Koob, G.F., Wall, T.L. & Bloom, F.E. Nucleus accumbens as a substrate for the aversive stimulus effects of opiate withdrawal.Psychopharmacology 98, 530–534 (1989). https://doi.org/10.1007/BF00441954

Download citation

• Received: 05 October 1988
• Accepted: 02 February 1989
• Issue Date: August 1989
• DOI: https://doi.org/10.1007/BF00441954

Key words