CRF-CRF1 system activation mediates withdrawal-induced increases in nicotine self-administration in nicotine-dependent rats.
Nicotine, the main psychoactive ingredient of tobacco, induces negative emotional symptoms during abstinence that contribute to a profound craving for nicotine. However, the neurobiological mechanisms underlying how nicotine produces dependence remains poorly understood. We demonstrate one mechanism for both the anxiety-like symptoms of withdrawal and excessive nicotine intake observed after abstinence, through recruitment of the extrahypothalamic stress peptide corticotropin-releasing factor (CRF) system and activation of CRF(1) receptors. Overactivation of the CRF-CRF(1) system may contribute to nicotine dependence and may represent a prominent target for investigating the vulnerability to tobacco addiction.
George
Olivier
O
Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA 92037, USA. ogeorge@scripps.edu
Ghozland
Sandy
S
Azar
Marc R
MR
Cottone
Pietro
P
Zorrilla
Eric P
EP
Parsons
Loren H
LH
O'Dell
Laura E
LE
Richardson
Heather N
HN
Koob
George F
GF
D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001007:Anxiety; D016739:Behavior, Addictive; D001522:Behavior, Animal / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D005247:Feeding Behavior / Q000187:drug effects; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009538:Nicotine / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D000099052:CRF Receptor, Type 1
D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; D008464:Mecamylamine; D009538:Nicotine; D003346:Corticotropin-Releasing Hormone