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Nicotine attenuates place aversion induced by naloxone in single-dose, morphine-treated rats

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Abstract

Rationale

Acute physical dependence refers to the withdrawal syndrome precipitated by an opioid antagonist administered several hours after either a single dose or a short-term infusion of an opioid agonist.

Objectives

We examined the mechanism of nicotine-induced attenuation of naloxone-precipitated withdrawal syndrome when used to produce an aversive motivational state in a place-conditioning paradigm.

Methods

The effect of nicotine was investigated through place aversion induced by naloxone in morphine-pretreated rats. Additionally, the mechanism of nicotine action in this model was explored specifically in relation to the dopaminergic system through the use of dopamine receptor antagonist and agonist.

Results

Place avoidance behavior was potently elicited by naloxone (0.5 mg/kg s.c.) 24 h after a single exposure to morphine (10 mg/kg s.c.). Avoidance behavior was attenuated by pretreatment with a 0.2-mg/kg dose of nicotine 15 min prior to naloxone administration. The effect of nicotine was completely blocked by mecamylamine, but not hexamethonium. The dopamine receptor antagonists haloperidol (0.05, 0.1 mg/kg, s.c.), SCH23390 (0.1 mg/kg, s.c.), raclopride (1.0 mg/kg, s.c.) and eticlopride (0.1 mg/kg, s.c.) showed effects similar to mecamylamine. Additionally, the dopamine receptor agonist apomorphine (0.03, 0.1, 0.3 mg/kg, s.c.) inhibited naloxone-induced place aversion in morphine-treated rats.

Conclusion

The inhibitory effect of nicotine on place aversion induced by naloxone-precipitated morphine withdrawal may involve a dopaminergic portion of the central nervous system.

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Acknowledgements

This study was supported, in part, by a Grant-in-Aid for Drug Abuse Research from the Ministry of Health and Welfare, Japan, and by a grant from the Smoking Research Foundation of Japan.

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Authors and Affiliations

  1. Division of Pharmacy, Ehime University Hospital, 454 Shitsukawa, Shigenobu-cho, 791-0295, Ehime, Onsen-gun, Japan

    Hiroaki Araki & Katsuya Suemaru

  2. Department of Hospital Pharmacy, Okayama University Medical School, 2-5-1 Shikata-cho, 700-8558, Okayama, Japan

    Ken-ya Kawakami, Yoshihisa Kitamura, Mari Nagata, Koujiro Futagami, Kazuhiko Shibata & Yutaka Gomita

  3. Department of Clinical Pharmaceutical Science, Graduate School of Natural Science and Technology, Okayama University, 1-1-1 Tsushima-naka, 700-8530, Okayama, Japan

    Chunyu Jin & Hiromu Kawasaki

Authors
  1. Hiroaki Araki
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  2. Ken-ya Kawakami
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  3. Chunyu Jin
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  4. Katsuya Suemaru
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  5. Yoshihisa Kitamura
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  6. Mari Nagata
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  7. Koujiro Futagami
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  8. Kazuhiko Shibata
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  9. Hiromu Kawasaki
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  10. Yutaka Gomita
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Corresponding author

Correspondence to Hiroaki Araki.

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Araki, H., Kawakami, Ky., Jin, C. et al. Nicotine attenuates place aversion induced by naloxone in single-dose, morphine-treated rats. Psychopharmacology 171, 398–404 (2004). https://doi.org/10.1007/s00213-003-1595-7

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  • DOI: https://doi.org/10.1007/s00213-003-1595-7

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