Effects of Volinanserin on Sleep and Wake Stages and the EEG Spectrum During Nicotine Withdrawal in Rats

Sleep disturbances, such as sleep onset latency and fragmentation commonly occur during nicotine intake and withdrawal. They may be one major factor in supporting relapse during smoking cessation. In a laboratory model of these disturbances, rats underwent surgical implantation of EEG and EMG electrodes. They were monitored and allowed to recover over several days, and a 24-hour baseline was recorded for sleep and wake stages, as well as the frequency spectrum of EEG activity. The rats were then implanted with an osmotic minipump infusing either saline or 9mg/kg/day nicotine bitartrate solution for one week. Seventeen hours after removal of the minipump, rats in their primary sleeping phase (lights on) were given an injection of either vehicle (20% DMSO and 20% Tween-80 in saline) or 3mg/kg volinanserin in that vehicle. The injection was repeated 12 hours later in their primary waking phase. EEG and EMG recordings were analyzed by KisseiComtec SleepSign Software and checked manually by the researcher. Compared with the non dependent controls, untreated nicotine withdrawal induced increased sleep wake fragmentation in the lights-off phase, and alterations in the power of several EEG frequency bands. There were trends for volinanserin to prevent the fragmentation and several of the alterations in band power. Inhibiting the 5-HT2A serotonin receptor with drugs like volinanserin might be a novel treatment approach to help nicotine users avoid sleep disturbances during tobacco cessation.