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.
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Acknowledgements
This research was supported by DA-03977 (BMS) from NIDA. We thank Ms Kathy McAllen, Ms Weihua Cheng, and Dr Wenyuan Zhao for their technical contributions.
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Chen, H., Fu, Y. & Sharp, B. Chronic Nicotine Self-Administration Augments Hypothalamic–Pituitary–Adrenal Responses to Mild Acute Stress. Neuropsychopharmacol 33, 721–730 (2008). https://doi.org/10.1038/sj.npp.1301466
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DOI: https://doi.org/10.1038/sj.npp.1301466
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