The CCK-B antagonist LY288513 blocks the effects of nicotine withdrawal on auditory startle.
In order to explore the potential clinical utility of CCK-B antagonists for the treatment of nicotine withdrawal symptoms, the auditory startle reflex was examined in rats undergoing withdrawal from the chronic administration of nicotine. Rats were exposed to nicotine continuously for 12 days (6 mg kg-1 day-1) via osmotic minipumps. After 12 days the pumps were removed and the animals allowed to go through spontaneous withdrawal for several days. Acute treatment with the CCK-B antagonist LY288513, at doses that have no effect on startle responses in naive rats, blocked the nicotine withdrawal-induced increase in the acoustic startle reflex. These results indicate that CCK-B antagonists may be an efficacious treatment for some nicotine withdrawal symptoms in man and may represent a novel pharmacotherapy for smoking cessation.
Rasmussen
K
K
Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Czachura
J F
JF
Kallman
M J
MJ
Helton
D R
DR
D000818:Animals; D006727:Hormone Antagonists / Q000494:pharmacology*; D008297:Male; D009538:Nicotine / Q000009:adverse effects*; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D013216:Reflex, Startle / Q000187:drug effects*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*
D006727:Hormone Antagonists; D011720:Pyrazoles; D011949:Receptors, Cholecystokinin; C074681:1-(4-bromophenylaminocarbonyl)-4,5-diphenyl-3-pyrazolidinone; D009538:Nicotine