Figure 1.

Simplified cartoon, summarizing the effects of chronic exposure to nicotine on excitatory and inhibitory neurotransmitter signaling regulated by nicotinic acetylcholine receptors in the nervous system. Chronic exposure to nicotine upregulates the α₇nAChR without desensitizing the receptor[13, 34], resulting in increased release and synthesis of excitatory neurotransmitters glutamate, dopamine, serotonin and noradrenaline stimulated by this receptor. Most of the stimulating neurological and psychological effects of these neurotransmitters are mediated by the activation of adenylyl cyclase downstream of Gα_s-coupled receptors. GABA normally balances these effects by inhibiting adenylyl cyclase downstream of the Gα_i-coupled GABA_BR[13, 54]. The α₄β₂nAChR that stimulates the release and synthesis of GABA is desensitized by chronic exposure to nicotine, thus virtually shutting down all inhibitory GABA signaling[54]. This imbalance in stimulatory and inhibitory brain functions has been implicated in nicotine addiction and withdrawal symptoms [13, 34, 53].