Abstract
Anxiety is a common symptom of nicotine withdrawal in humans, and may predict an inability to abstain from cigarette smoking. It is not clear if self-reports of anxiety during abstinence reflect increased baseline anxiety and/or increased responses to exogenous stressors. We hypothesized that nicotine withdrawal selectively exacerbates reactivity to aversive stimuli in rodents. Here, we investigated the effect of withdrawal from chronic nicotine administration (3.16 mg/kg per day base, delivered via subcutaneous osmotic minipumps) in the light-enhanced startle (LES) test in Wistar rats. In this procedure, baseline startle responding in the dark is compared to startle responding when the chamber is brightly lit. Bright illumination is aversive for rats and potentiates the startle response. Hence, this procedure allows comparisons of withdrawal effects on startle reactivity between relatively neutral and stressful contexts. We found that spontaneous nicotine withdrawal (24 h post-pump removal) did not influence baseline startle responding, but produced a selective increase in LES. Precipitated nicotine withdrawal through injections of one of two nicotinic acetylcholine receptor (nAChR) antagonists, dihydro-β-erythroidine hydrobromide (DHβE: 0, 1.5, 3, or 6 mg/kg) or mecamylamine (0, 1, 2, or 4 mg/kg), did not influence baseline startle responding or LES. These results suggest that spontaneous nicotine withdrawal selectively potentiates responses to anxiogenic stimuli, but does not by itself produce a strong anxiogenic effect. These findings support the hypothesis that nicotine withdrawal exacerbates stress responding, and indicate LES may be a useful model to examine withdrawal effects on anxiety.
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Acknowledgements
We thank Mr Richard Sharp for technical assistance and Mr Mike Arends for editorial assistance. This work was supported by National Institute of Mental Health grant MH074697 and the VISN22 Veterans Administration Mental Illness Research and Clinical Core (MAG), Veterans Administration Center for Stress and Mental Health and MH076850 (VBR), National Institute on Drug Abuse grant DA11946, and Tobacco-Related Disease Research Program grant 15RT-0022 (AM).
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SJ and AM declare that, except for income received from their primary employers, no financial support or compensation has been received from any individual or corporate entity over the past 3 years of research or professional service, and they have no personal financial holdings that could be perceived as constituting a potential conflict of interest. VBR declares that over the past 3 years she has received compensation from Addex and San Diego Instruments. MAG declares that over the past 3 years he has received compensation from Abbott, Acadia, Addex, Amgen, AstraZeneca, Bristol-Myers Squibb, Jazz, Organon, Nura, Serono, and Wyeth-Ayerst and holds an equity interest in San Diego Instruments.
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Jonkman, S., Risbrough, V., Geyer, M. et al. Spontaneous Nicotine Withdrawal Potentiates the Effects of Stress in Rats. Neuropsychopharmacol 33, 2131–2138 (2008). https://doi.org/10.1038/sj.npp.1301607
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DOI: https://doi.org/10.1038/sj.npp.1301607
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