Loss of Nicotine-Induced Behavioral Sensitization in μ-Opioid Receptor Knockout Mice

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, nicotinetreated 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.