Diminished nicotine withdrawal in adolescent rats: implications for vulnerability to addiction.
BACKGROUND
Enhanced reinforcing effects of nicotine during adolescence appear to contribute to the rapid development of dependence in this age group. However, the contribution of nicotine withdrawal to dependence in adolescents is unclear.


OBJECTIVE
We compared motivational and somatic signs of nicotine withdrawal in adolescent and adult rats.


METHODS
In experiment 1, motivational signs of nicotine withdrawal were compared using intracranial self-stimulation procedures after administration of mecamylamine (1.5 mg/kg, i.p.) in adolescent and adult rats made dependent on nicotine (9 mg/kg/day). Somatic signs of withdrawal were compared in two experiments using various doses of nicotine (adolescent doses: 0, 1.6, 3.2, 4.7 mg/kg/day; adult doses: 0, 1, 2.1, 3.2 mg/kg/day, expressed as nicotine base) to produce dependence and one dose of mecamylamine (1.5 mg/kg, i.p.) to precipitate withdrawal (experiment 2) and in a subsequent experiment, using various doses of mecamylamine (0, 0.75, 1.5, 3.0 mg/kg, i.p.) to precipitate withdrawal and a dose of nicotine (adolescent dose: 4.7 mg/kg/day; adult dose: 3.2 mg/kg/day) that produced equivalent nicotine blood levels in these age groups (experiment 3).


RESULTS
Adolescents did not display the decreases in brain reward function observed in adults experiencing withdrawal, and displayed fewer somatic signs of nicotine withdrawal relative to adults regardless of the dosing procedure used.


CONCLUSIONS
The negative effects of nicotine withdrawal are lower during adolescence relative to later periods of development. Both the enhanced rewarding effects and the diminished nicotine withdrawal likely contribute to the rapid development of nicotine use during adolescence.
O'Dell
Laura E
LE
Molecular and Integrative Neuroscience Department, CVN-7, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Bruijnzeel
Adie W
AW
Smith
Ron T
RT
Parsons
Loren H
LH
Merves
Michele L
ML
Goldberger
Bruce A
BA
Richardson
Heather N
HN
Koob
George F
GF
Markou
Athina
A
D000367:Age Factors; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003367:Cotinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009538:Nicotine / Q000009:adverse effects* / Q000037:antagonists & inhibitors / Q000097:blood; D018733:Nicotinic Antagonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D012653:Self Stimulation; D012684:Sensory Thresholds / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000097:blood / Q000523:psychology*; D014029:Tobacco Use Disorder / Q000523:psychology*
D018733:Nicotinic Antagonists; D008464:Mecamylamine; D009538:Nicotine; D003367:Cotinine