Nicotine withdrawal in adolescent and adult rats.
Previous research with animal models has demonstrated that adolescent rats display heightened sensitivity to the reinforcing and stimulant effects of nicotine relative to adult rats. Little work has focused on the response of adolescent rats to measures of nicotine withdrawal. To test the hypothesis that adolescent rats may be differentially sensitive to withdrawal relative to their adult counterparts, the present study was designed to compare precipitated withdrawal in adolescent and adult rats following chronic nicotine administration. Adult and adolescent rats were prepared with subcutaneous osmotic minipumps that delivered either saline or nicotine (9 mg/kg per day, salt; N =12 per group). All rats were challenged with the nicotinic receptor antagonist mecamylamine (1.5 mg/kg) on day 7 of chronic nicotine treatment. Twenty minutes after the injection, overt somatic signs of withdrawal (i.e., eye blinks, writhes, body shakes, teeth chatter, gasps, and ptosis) were recorded for 10 min. Adult rats were observed on postnatal day 73-77, and adolescent rats were tested on postnatal day 36-40. The results revealed a robust increase in mecamylamine-induced withdrawal signs in adult rats receiving chronic nicotine relative to adult rats receiving saline. In contrast, mecamylamine did not precipitate withdrawal signs in adolescent rats receiving chronic nicotine. These results indicate that there is decreased sensitivity to the somatic aspects of nicotine withdrawal in adolescent rats that may maximize the reinforcing effects of nicotine during adolescence by minimizing the aversive effects of abstinence.
O'Dell
Laura E
LE
Department of Neuropharmacology, CVN-7, The Scripps Research Institute, 10550 North Torrey Pines Rd., La Jolla, CA 92037, USA. gkoob@scripps.edu
Bruijnzeel
Adrie W
AW
Ghozland
Sandy
S
Markou
Athina
A
Koob
George F
GF
D000293:Adolescent; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001767:Blinking / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D006801:Humans; D015918:Infusion Pumps, Implantable; D008297:Male; D008464:Mecamylamine / Q000008:administration & dosage; D009538:Nicotine / Q000008:administration & dosage / Q000009:adverse effects*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000009:adverse effects*; D018733:Nicotinic Antagonists / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000209:etiology*; D014029:Tobacco Use Disorder / Q000188:drug therapy
D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D008464:Mecamylamine; D009538:Nicotine