Nicotine and its withdrawal alter feeding induced by paraventricular hypothalamic injections of neuropeptide Y in Sprague-Dawley rats

Rationale: Cigarette smoking produces feeding and weight suppression in humans that often rebound following cessation. Nicotine (NIC) administration produces similar effects in rats, but the neural mechanisms responsible are not fully known. Recent evidence shows that hypothalamic levels of neuropeptide Y (NPY) change with NIC administration. Infusions of NPY into the paraventricular nucleus of the hypothalamus (PVN), which normally produce robust feeding, were used to investigate changes in the PVN-NPY system that may contribute to NIC's effects on energy balance. Objective: To characterize potential differences in PVN-NPY-induced feeding during NIC treatment versus withdrawal. Methods: Three groups of female rats (n=66) bearing unilateral PVN cannulae were implanted for 14 days with subcutaneous Alzet mini-pumps containing NIC (0, 6, or 12 mg/kg per day). Dark-onset (1800-2000 hours) NPY feeding tests occurred five times: pre-implant, 2 days and 12 days post-implant and 2 days and 8 days after implant removal. Feeding tests consisted of 1 h of pre-feeding prior to lights off, then two 1-h measures of feeding after PVN injections of 0.4 μl saline or NPY (78 pmol, 235 pmol). Results: NIC initially suppressed body weight gain, followed by steady recovery that was briefly exaggerated after withdrawing NIC. Daily feeding was acutely suppressed by NIC but acutely potentiated after NIC cessation. PVN-NPY-induced feeding was suppressed by both doses of NIC 2 days after pump implant, elevated 2 days after pump removal, but returned to pre-NIC levels 8 days after pump removal. Conclusions: These findings provide behavioral support that changes in PVN-NPY neurotransmission may play a functional role in the food intake and weight-modulating effects of NIC.