Chronic Nicotine Augments Responses to Mild Acute Stress

http://www.nature.com/npp/journal/vaop/ncurrent/abs/1301466a.html;jsessionid=01E4F9D742D9FB03EA2E191CBFC91B05
Neuropsychopharmacology advance online publication 6 June 2007; doi: 10.1038/sj.npp.1301466
Chronic Nicotine Self-Administration Augments Hypothalamic–Pituitary–Adrenal Responses to Mild Acute Stress
Hao Chen1, Yitong Fu1 and Burt M Sharp1
1Department of Pharmacology, University of Tennessee Health Science Center, Memphis, TN, USA
Correspondence: Dr BM Sharp, Department of Pharmacology, University of Tennessee Health Science Center, 874 Union Avenue, Memphis, TN 38163, USA. Tel: +1 901 448 6000; Fax: +1 901 448 7206; E-mail: bsharp@utmem.edu
Received 16 February 2007; Revised 5 April 2007; Accepted 30 April 2007; Published online 6 June 2007.

Abstract
We investigated the effect of chronic nicotine self-administration (SA) on hypothalamic–pituitary–adrenal (HPA) hormonal responses to acute stressors. Adult male Sprague–Dawley rats were given access to nicotine (0.03 mg/kg) for 23 h per day for 20 days. On day 1 of acquisition of nicotine SA, plasma levels of both adrenocorticotropin and corticosterone were significantly increased 15–30 min after the first dose of nicotine. These hormonal changes were no longer significant on day 3, when adrenocorticotropin levels were <60 pg/ml and corticosterone levels were <110 ng/ml during the hour after the first dose of nicotine. Chronic nicotine SA (20 days) significantly augmented (2–3-fold) both hormonal responses to mild foot shock stress (0.6 mA, 0.5 s per shock, 5 shocks per 5 min), but did not affect hormonal responses to moderate shock (1.2 mA, 0.5 s per shock, 5 shocks per 5 min), lipopolysaccharide or immobilization. Similar data were obtained in Lewis rats. These results provide further support for the concept that chronic nicotine SA is a stressor. In alignment with the effects of other stressors, nicotine activated the HPA axis on the first day of SA, but desensitization occurred with repeated exposure. Furthermore, chronic nicotine SA selectively cross-sensitized the HPA response to a novel stressor. These observations suggest that nicotine may selectively increase the HPA response to stressors in human smokers.
Keywords:
nicotine self-administration, stress, ACTH, corticosterone, psychological stress, physical stress