Loss of nicotine‐induced behavioral sensitization in μ‐opioid receptor knockout mice

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Abstract
Repeated administration of nicotine produces behavioral sensitization. However, the possible mechanism of behavioral sensitization to nicotine remains unclear. The present study was undertaken in μ‐opioid receptor knockout mice, to examine the hypothesis that μ‐opioid receptors play a crucial role in behavioral sensitization to nicotine. All mice received saline or nicotine (0.05 mg/kg, s.c) twice a day for 7 consecutive days. The mice remained drug free for 3 days and on day 11 each group was challenged with saline or nicotine (0.05 mg/kg, s.c.). On day 1, it was observed that the single injection of nicotine (0.05 mg/kg, s.c.) did not influence locomotor activity in either μ‐opioid receptor knockout or in wildtype mice. On day 7 (24 h after mice had been treated twice daily for 6 consecutive days with an injection of 0.05 mg/kg of nicotine), the mice were challenged with a single injection of nicotine, which produced behavioral sensitization in the wildtype but not in μ‐opioid receptor knockout mice. On day 11, following 3 days of withdrawal after the second injection of nicotine on day 7, nicotine‐treated mice were challenged with a single injection of nicotine and showed the behavioral sensitization of wildtype. However, nicotine challenge did not induce behavioral sensitization in μ‐opioid receptor knockout mice. Our data indicate that a lack of μ‐opioid receptors can inhibit the effects of nicotine‐induced behavioral sensitization. This result strongly suggests that the μ‐opioid receptor plays an important role in behavioral sensitization to nicotine. Synapse 51:219–223, 2004.