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Spectral Confocal Imaging of Fluorescently tagged Nicotinic Receptors in Knock-in Mice with Chronic Nicotine Administration
Published on: February 10, 2012
Minocycline reduced craving for cigarettes but did not affect smoking or intravenous nicotine responses in humans
Mehmet Sofuoglu1, Andrew J Waters, Marc Mooney
1Yale University, School of Medicine, Department of Psychiatry, West Haven, CT, USA. Mehmet.Sofuoglu@yale.edu
Abstract:
In recent preclinical studies, the role of nitric oxide (NO) in nicotine dependence has become increasingly evident. Inhibition of NO synthesis blocks acquisition of conditioned place preference, and attenuates the nicotine abstinence syndrome in rodents. These findings have not been followed up in human studies. In order to obtain preliminary data on NO inhibition in human smokers, we conducted a randomized, double-blind, crossover study (N=12) of minocycline, a tetracycline derivative antibiotic, that inhibits the neuronal nitric oxide (NO) synthase enzyme with resultant inhibition of NO production. Medication effects were assessed through a smoking choice procedure as well as subjective and physiological responses to nicotine administered via the intravenous route (IV). Minocycline treatment did not affect smoking self-administration in our choice procedure and did not affect most of the subjective responses to IV nicotine or sample smoking. Following IV nicotine administration, there was a greater reduction in craving for cigarettes under minocycline, compared to placebo. Similarly, smokers had greater reduction in their craving for cigarettes following sample smoking under minocycline treatment. These findings provide limited support for the potential use of minocycline as a treatment of nicotine dependence.
Insights
Minocycline, an antibiotic, showed potential in reducing cigarette cravings in smokers by inhibiting nitric oxide (NO) production. Further research is needed to confirm its efficacy for nicotine dependence treatment.
Area of Science:
- Neuroscience
- Pharmacology
- Addiction Medicine
Background:
- Preclinical studies suggest nitric oxide (NO) plays a crucial role in nicotine dependence.
- Inhibition of NO synthesis in rodents has been shown to block nicotine reward and reduce withdrawal symptoms.
- Human studies investigating NO inhibition for nicotine dependence are lacking.
Purpose of the Study:
- To obtain preliminary data on the effects of NO inhibition in human smokers.
- To assess the impact of minocycline, a nitric oxide synthase inhibitor, on nicotine dependence.
- To evaluate minocycline's effects on smoking behavior and responses to nicotine.
Main Methods:
- A randomized, double-blind, crossover study involving 12 human smokers.
- Administration of minocycline, an antibiotic that inhibits neuronal nitric oxide synthase.
- Assessment of smoking self-administration, subjective responses, and physiological effects of intravenous nicotine.
Main Results:
- Minocycline did not alter smoking self-administration in a choice procedure.
- Most subjective responses to intravenous nicotine and sample smoking were unaffected by minocycline.
- Minocycline significantly reduced cigarette craving following both intravenous nicotine administration and sample smoking, compared to placebo.
Conclusions:
- Minocycline demonstrated a potential to reduce cigarette cravings in smokers.
- These findings offer limited support for minocycline as a therapeutic agent for nicotine dependence.
- Further investigation is warranted to explore the clinical utility of minocycline in smoking cessation programs.
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