Abstract
Few attempts to quit smoking are successful, making current interventions relatively ineffective. Evidence shows that exercise decreases nicotine withdrawal symptoms in humans, but the mechanism is unclear. Part of this thesis aimed to explore the mechanisms underpinning the effect of exercise on nicotine withdrawal in both human and animal models of nicotine addiction. The role of perception of exercise intensity was investigated in temporarily abstinent smokers. Perceived and objective moderate intensity exercise and passive waiting all reduced withdrawal symptoms, and salivary cortisol was attenuated compared with pre-abstinence levels, but there was no difference between any of the interventions. These results indicate that exercise may reduce withdrawal by acting as a distraction, but does not preclude biochemical mechanisms from playing a role. Nicotine-treated mice undertaking 2 or 24 hrs/day running wheel access, demonstrated reduced mecamylamine-precipitated withdrawal symptoms compared with sedentary mice, indicating that even a low level of exercise aids in reducing withdrawal symptoms. This was accompanied by a significant increase in hippocampal α7 nicotinic receptors (nAChRs), implicating the α7 nAChR in a mechanism underlying the effect of exercise in nicotine withdrawal. The effect of nicotine on nAChR and oxytocin receptor (OTR) binding in a mouse model of schizophrenia was investigated using mice with a G72 protein insertion (G72Tg). Nicotine reversed social cognitive deficits in G72Tg mice, associated with attenuation of α7 nAChR and OTR binding in the cingulate cortex by nicotine in G72Tg mice. These results implicate both α7 nAChRs and OTR as targets for the development of pharmacotherapies for the treatment of social and cognitive deficits in schizophrenia. All together, the results in this thesis show that the α7 nAChR may be involved in modulating behavioural responses in nicotine addiction. Furthermore, dysregulation of α7 and OT receptors may underlie the mechanism of cognitive and social deficits in schizophrenia.