title: Chronic nicotine self-administration augments hypothalamic-pituitary-adrenal responses to mild acute stress.
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.
authors.affiliation: Department of Pharmacology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.forename: Yitong
authors.initials: Y
authors.lastname: Fu
authors.forename: Burt M
authors.initials: BM
authors.lastname: Sharp
mesh_terms: D000208:Acute Disease; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004597:Electroshock / Q000009:adverse effects; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000008:administration & dosage*; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical / Q000009:adverse effects; D012646:Self Administration / Q000379:methods; D013315:Stress, Psychological / Q000097:blood* / Q000188:drug therapy / Q000209:etiology; D013997:Time Factors
chemical_list: D008070:Lipopolysaccharides; D018722:Nicotinic Agonists; D009538:Nicotine; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone