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Updated: Aug 12, 2026
Spectral Confocal Imaging of Fluorescently tagged Nicotinic Receptors in Knock-in Mice with Chronic Nicotine Administration
Published on: February 10, 2012
Loss of nicotine-induced behavioral sensitization in micro-opioid receptor knockout mice
Ji-Hoon Yoo1, Seok-Yong Lee, Horace H Loh
1Department of Pharmacology College of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
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 micro-opioid receptor knockout mice, to examine the hypothesis that micro-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 micro-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 micro-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 micro-opioid receptor knockout mice. Our data indicate that a lack of micro-opioid receptors can inhibit the effects of nicotine-induced behavioral sensitization. This result strongly suggests that the micro-opioid receptor plays an important role in behavioral sensitization to nicotine.
Insights
Micro-opioid receptors are crucial for nicotine-induced behavioral sensitization. Mice lacking these receptors did not develop sensitization, suggesting a key role for micro-opioid receptors in this nicotine effect.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- Repeated nicotine administration leads to behavioral sensitization, a phenomenon where drug effects intensify with repeated exposure.
- The precise neurobiological mechanisms underlying nicotine-induced behavioral sensitization remain incompletely understood.
Purpose of the Study:
- To investigate the role of micro-opioid receptors in the development of behavioral sensitization to nicotine.
- To test the hypothesis that micro-opioid receptors are essential for nicotine-induced behavioral sensitization.
Main Methods:
- Utilized micro-opioid receptor knockout mice and their wildtype littermates.
- Administered nicotine (0.05 mg/kg, s.c.) or saline twice daily for 7 days.
- Challenged mice with nicotine on days 7 and 11 to assess locomotor activity and behavioral sensitization.
Main Results:
- Single nicotine injections did not affect locomotor activity in either genotype.
- Wildtype mice exhibited behavioral sensitization to nicotine after repeated administration and challenge.
- Micro-opioid receptor knockout mice did not show behavioral sensitization to nicotine, even after repeated administration and challenge.
Conclusions:
- The absence of micro-opioid receptors significantly inhibits nicotine-induced behavioral sensitization.
- These findings strongly implicate the micro-opioid receptor system as a critical component in the neurobiological pathways mediating behavioral sensitization to nicotine.
