Abstract

Nicotine withdrawal is associated with dysphoria and depression in humans. In rats, withdrawal from amphetamine, cocaine, or morphine attenuates the motivation to respond for rewarding electrical brain stimulation. It has been proposed that such attenuation of brain stimulation reward reflects opponent-process depression of brain reward circuitry and underlies the dysphoric symptoms of drug withdrawal in humans. In the present study the rate-frequency variant of the curve-shift paradigm was used to examine the effects of nicotine withdrawal on brain stimulation reward. Animals were injected with either saline, 0.5 or 1.5 mg/kg of nicotine once on the first day of treatment then twice daily for the next 13 days (equaling a dose of 1.0 or 3.0 mg/kg/day) and on the morning of the final day (day 15). Brain stimulation reward thresholds were then determined periodically for 24 hours. Withdrawal from 3.0 mg/kg/day of nicotine increased the frequency required to sustain responding to approximately 132% of baseline. This increase was evident 8 hours after the last nicotine injection and remained so for 24 hours. Nicotine withdrawal did not effect maximal response rates. There was no effect of withdrawal from 1.0 mg/kg/day of nicotine or from daily saline. The present study provides evidence that nicotine withdrawal attenuates brain stimulation reward in a manner similar to amphetamine and morphine withdrawal. This evidence supports the view that depression of the reward system is a withdrawal symptom common to several classes of drugs.