Bupropion attenuates nicotine abstinence syndrome in the rat.
BACKGROUND
Bupropion reduces discomfort and craving associated with smoking cessation. This study determined whether a rat model of nicotine dependence could detect such nicotine abstinence-alleviating effects.


OBJECTIVE
Experiments determined whether the abstinence-alleviating effects of bupropion were detectable by (1) behavioral abstinence signs precipitated by the nicotinic antagonist mecamylamine, (2) place aversion conditioned to mecamylamine-precipitated nicotine abstinence, and (3) spontaneous behavioral abstinence signs after abrupt nicotine withdrawal.


METHODS
In experiments 1 and 2, nicotine-dependent rats were coinfused for 7 days with 3.15 mg/kg/day nicotine and 20 mg/kg/day bupropion or with nicotine alone. They were then challenged with 1 mg/kg mecamylamine and observed for behavioral abstinence signs (experiment 1) or place aversion conditioned to precipitated abstinence (experiment 2). In experiment 3, rats were nicotine-infused for 7 days as above. A day after termination of nicotine infusion, rats were observed for spontaneous nicotine abstinence signs before and after injection with saline or bupropion.


RESULTS
In experiment 1, rats coinfused with nicotine and bupropion had significantly fewer mecamylamine-precipitated abstinence signs than rats infused with nicotine alone but similar numbers to rats infused with saline alone. In experiment 2, bupropion pretreatment significantly reduced the aversiveness of mecamylamine-precipitated nicotine abstinence. In experiment 3, a single bupropion injection dose-dependently alleviated spontaneous nicotine abstinence syndrome.


CONCLUSIONS
These results suggest that these rat models of nicotine dependence and abstinence syndrome may be useful in detecting nicotine abstinence-alleviating effects of potential medications for smoking cessation. The effects of acute bupropion administration raise interesting questions regarding bupropion's mechanism of action.
Malin
David H
DH
University of Houston-Clear Lake, P.O. Box 237, 2700 Bay Area Blvd., Houston, TX 77058, USA. malin@cl.uh.edu
Lake
J Ronald
JR
Smith
Tanya D
TD
Khambati
Habil N
HN
Meyers-Paal
Rhonda L
RL
Montellano
Ana L
AL
Jennings
Ryan E
RE
Erwin
Daniel S
DS
Presley
Stacey E
SE
Perales
Barbara A
BA
D000818:Animals; D001245:Association Learning / Q000187:drug effects; D001362:Avoidance Learning / Q000187:drug effects*; D016642:Bupropion / Q000494:pharmacology*; D003214:Conditioning, Classical / Q000187:drug effects*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009538:Nicotine / Q000008:administration & dosage / Q000009:adverse effects*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011292:Premedication; D051381:Rats; D017207:Rats, Sprague-Dawley; D012931:Social Environment; D013375:Substance Withdrawal Syndrome / Q000523:psychology*
D018765:Dopamine Uptake Inhibitors; D018733:Nicotinic Antagonists; D016642:Bupropion; D008464:Mecamylamine; D009538:Nicotine