Affiliation:
1. McLean Hospital, Harvard Medical School, Belmont, MA
Abstract
Abstract
Background
Tobacco use is prevalent in individuals who are routinely exposed to stress. However, little is known about how nicotine affects responses to trauma. We examined in rats how nicotine exposure affects fear conditioning, a procedure often used to study stress-related psychiatric illness.
Methods
We examined 2 methods of nicotine exposure: self-administration, modeling voluntary use, and experimenter-programmed subcutaneous administration, modeling medicinal administration (nicotine patch). For self-administered nicotine, rats trained to self-administer nicotine i.v. were fear conditioned (via light cue preceding foot-shock) either immediately after a 12-hour self-administration session or 12 hours later during a period with somatic signs of nicotine withdrawal. For experimenter-delivered nicotine, rats were conditioned after 1–21 days of nicotine delivered by programmable (12 hours on) subcutaneous mini-pumps. Tests to evaluate acoustic startle responses to the conditioning environment (context-potentiated startle) and in the presence or absence of the light cue (fear-potentiated startle) occurred after a 10-day period.
Results
Rats fear conditioned immediately after nicotine self-administration showed reduced responses to the shock-associated context, whereas those trained during nicotine withdrawal showed exaggerated responses. Experimenter-programmed nicotine produced effects qualitatively similar to those seen with self-administered nicotine.
Conclusions
Self-administration or experimenter-programmed delivery of nicotine immediately before exposure to aversive events can reduce conditioned fear responses. In contrast, exposure to aversive events during nicotine withdrawal exacerbates fear responses. These studies raise the possibility of developing safe and effective methods to deliver nicotine or related drugs to mitigate the effects of stress while also highlighting the importance of preventing withdrawal in nicotine-dependent individuals.
Publisher
Oxford University Press (OUP)
Subject
Pharmacology (medical),Psychiatry and Mental health,Pharmacology
Reference51 articles.
1. Diagnostic and statistical manual of mental disorders: DSM-5;American Psychiatric Association,2013
2. Subjective effects of transdermal nicotine among nonsmokers;Ashare;Exp Clin Psychopharmacol,2010
3. The effects of transdermal nicotine on cognition in nonsmokers with schizophrenia and nonpsychiatric controls;Barr;Neuropsychopharmacology,2008
4. Potentiation of lateral hypothalamic and midline mesencephalic brain stimulation reinforcement by nicotine: examination of repeated treatment;Bauco;J Pharmacol Exp Ther,1994
5. Behavioral pharmacology of novel kappa opioid receptor antagonists in rats;Becker;Neuropsychopharmacology,2019
Cited by
6 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献