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Eur J Pharmacol. 2008 Jun 10;587(1-3):169-74. doi: 10.1016/j.ejphar.2008.03.028. Epub 2008 Apr 1.

Morphine-nicotine interaction in conditioned place preference in mice after chronic nicotine exposure.

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Division of Pharmacology and Toxicology, Faculty of Pharmacy, P.O. Box 56 (Viikinkaari 5 E), University of Helsinki, FI-00014, Finland.


Previously we found that morphine's effects on locomotor activity and brain dopamine metabolism were enhanced in mice after cessation of 7-week oral nicotine treatment. In the present experiments we show that such chronic nicotine exposure cross-sensitizes NMRI mice to the reinforcing effect of morphine in the conditioned place preference paradigm. The nicotine-treated mice developed conditioned place preference after being conditioned twice with morphine 5 mg/kg s.c. whereas in control mice a higher dose (10 mg/kg) of morphine was required. Since the reinforcing effect of morphine is mediated via micro-opioid receptors we used [3H]DAMGO autoradiography to study whether the number (B(max)) or affinity (K(D)) of mu-opioid receptors in the mouse brain are affected following chronic nicotine exposure. However, no changes were found in the number or affinity of micro-opioid receptors in any of the brain areas studied. Neither did we find alterations in the functional activity of mu-opioid receptors studied by [35S]GTPgammaS-binding. In conclusion, chronic oral nicotine treatment augments the reinforcing effects of morphine in mice, and this cross-sensitization does not seem to be mediated by micro-opioid receptors.

[Indexed for MEDLINE]

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