SEROTONIN-1A ANTAGONISTS ATTENUATE THE EFFECTS OF NICOTINE WITHDRAWALON THE AUDITORY STARTLE RESPONSE

Withdrawal from the chronic administration of nicotine has previously been shown to lead to an enhanced auditory startle response in rats. I n order to explore the neuropharmacology and neurophysiology underlyin g this phenomenon, we examined the effects of various Ei-hydroxytrypta mine (5-HT)-1A antagonists and agonists on the nicotine-withdrawal-enh anced auditory startle response in male rats. Animals were treated wit h nicotine (6 mg/kg/day nicotine base, via subcutaneously implanted os motic minipumps) for 12 days. After 12 days the pumps were removed and the animals allowed to undergo spontaneous withdrawal for several day s. In agreement with previous results, nicotine withdrawal led to a si gnificant elevation of the auditory startle response. Pretreatment wit h the 5-HT-1A agonists (+)8-OH-DPAT (0.001-0.1 mg/kg) and LY274600 (0. 3-3.0 mg/kg) either had no affect or exacerbated the nicotine-withdraw al-enhanced startle response. Pretreatment with the 5-HT-1A antagonist s NAN-190 (1-3 mg/kg), LY206130 (1-10 mg/kg), or WAY-100635 (0.1-1.0 m g/kg) blocked the increase in the startle response caused by nicotine withdrawal at doses that had no effect on baseline startle responses. These data indicate that 5-HT-1A receptors play a role in the neurophy siology of nicotine withdrawal. In addition, 5-HT-1A antagonists may b e able to relieve some nicotine withdrawal symptoms in man and may rep resent a novel pharmacotherapy for smoking cessation. (C) 1997 Wiley-L iss, Inc.