Nicotine self-administration diminishes stress-induced norepinephrine secretion but augments adrenergic-responsiveness in the hypothalamic paraventricular nucleus and enhances adrenocorticotropic hormone and corticosterone release.
Chronic nicotine self-administration augments the thalamo-pituitary-adrenal (HPA) responses to stress. Altered neuropeptide expression within corticotropin-releasing factor (CRF) neurons in the hypothalamic paraventricular nucleus (PVN) contributes to this enhanced HPA response to stress. Herein, we determined the role of norepinephrine, a primary regulator of CRF neurons, in the responses to footshock during nicotine self-administration. On day 12-15 of self-administration, microdialysis showed nicotine reduced PVN norepinephrine release by footshock (< 50% of saline). Yet, the reduction in footshock-induced adrenocorticotropic hormone and corticosterone secretion because of intra-PVN prazosin (alpha(1) adrenergic antagonist) was significantly greater in rats self-administering nicotine (2-fold) than saline. Additionally, PVN phenylephrine (alpha(1) agonist) stimulated adrenocorticotropic hormone and corticosterone release to a similar extent in unstressed rats self-administering nicotine or saline. Nicotine self-administration also decreased footshock-induced c-Fos expression in the nucleus of the solitary tract-A2/C2 catecholaminergic neurons that project to the PVN. Therefore, footshock-induced nucleus of the solitary tract activation and PVN norepinephrine input are both attenuated by nicotine self-administration, yet PVN CRF neurons are more responsive to alpha(1) stimulation, but only during stress. This plasticity in noradrenergic regulation of PVN CRF neurons provides a new mechanism contributing to the HPA sensitization to stress by nicotine self-administration and smoking.
Yu
Guoliang
G
Department of Pharmacology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Sharp
Burt M
BM
D018663:Adrenergic Agents / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D004563:Electrochemistry / Q000379:methods; D004597:Electroshock / Q000009:adverse effects; D008297:Male; D017551:Microdialysis / Q000379:methods; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration / Q000379:methods; D017552:Solitary Nucleus / Q000378:metabolism; D013315:Stress, Psychological / Q000188:drug therapy / Q000209:etiology; D013997:Time Factors
D018663:Adrenergic Agents; D018722:Nicotinic Agonists; D016760:Proto-Oncogene Proteins c-fos; D009538:Nicotine; D000324:Adrenocorticotropic Hormone; D004299:Dopamine beta-Hydroxylase; D003345:Corticosterone; D009638:Norepinephrine