Morphine–nicotine interaction in conditioned place preference in mice after chronic nicotine exposure

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 µ-opioid receptors we used [3H]DAMGO autoradiography to study whether the number (Bmax) or affinity (KD) of µ-opioid receptors in the mouse brain are affected following chronic nicotine exposure. However, no changes were found in the number or affinity of µ-opioid receptors in any of the brain areas studied. Neither did we find alterations in the functional activity of µ-opioid receptors studied by [35S]GTPγS-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 µ-opioid receptors.