NICOTINE WITHDRAWAL LEADS TO INCREASED SENSITIVITY OF SEROTONERGIC NEURONS TO THE 5-HT1A AGONIST 8-OH-DPAT

In order to explore the neurophysiology of nicotine withdrawal, we exa mined the activity of serotonergic neurons in the dorsal raphe nucleus in rats undergoing withdrawal from chronic exposure to nicotine. Anim als were exposed to nicotine (6 mg/kg per day base) via SC implanted o smotic minipumps. After 12 days the pumps were removed and the animals allowed to go through spontaneous withdrawal. Rats were anesthetized on various days of the procedure and the effect of the 5-hydroxytrypta mine (5-HT)-1A agonist 8-OH-DPAT on the single-unit activity of seroto nergic neurons in the dorsal raphe nucleus was examined. The sensitivi ty of serotonergic neurons to 8-OH-DPAT was not changed by the chronic administration of nicotine or saline; slightly increased on day 2 of withdrawal; significantly increased on days 3 and 4 of withdrawal; and no longer significantly increased by day 7 of withdrawal. These resul ts indicate that serotonergic neurons in the dorsal raphe nucleus have an increased sensitivity to systemically administered 8-OH-DPAT in ra ts undergoing nicotine withdrawal and that the serotonergic system may play a role in the symptoms of nicotine withdrawal.