Nicotine and its withdrawal modify dorsal raphe 8-hydroxy-2-(di-n-propylamino) tetralin feeding

Nicotine (NIC) and its withdrawal modify dorsal raphe (DR) serotonin (5-HT) neurotransmission in ways that may contribute to the body weight loss vs. gain associated with cigarette smoking vs. cessation, respectively. Modifications in feeding to DR infusions of the 5-HT-1A receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), were used to characterize these potential relationships in the DR-5-HT system during NIC administration vs. withdrawal. Two groups of female rats (total N=45) were implanted for 14 days with subcutaneous Alzet minipumps containing NIC (6 mg/kg/day) or saline. Mid-light cycle (1300-1500 h) 8-OH-DPAT feeding tests occurred three times: (1) 2 days after pump implant, (2) 12 days after pump implant, and (3) 2 days after pump removal. Each feeding test consisted of a 1-h measure of pre-feeding, then a 1-h measure of feeding after DR injection of 8-OH-DPAT (0.6 nmol) or 0.4 microl saline. NIC administration produced acute hypophagia, weight loss, and attenuated 8-OH-DPAT-induced feeding. NIC withdrawal produced acute hyperphagia, weight gain, and a transient increase in 8-OH-DPAT feeding. These findings provide behavioral evidence that systemic NIC modifies the DR 5-HT system in ways that may contribute to NIC's ability to alter feeding and body weight.