Exposure to Commercial Cigarette Smoke Produces Psychomotor Sensitization via Hyperstimulation of Glutamate Response in the Dorsal Striatum

Cigarette smoke is a highly complex mixture of nicotine and non-nicotine constituents. Exposure to cigarette smoke enhances tobacco dependence by potentiating glutamatergic neurotransmission via stimulation of nicotinic acetylcholine receptors (nAChRs). We investigated the effects of nicotine and non-nicotine alkaloids in the cigarette smoke condensates extracted from two commercial cigarette brands in South Korea (KCSC A and KCSC B) on psychomotor behaviors and glutamate levels in the dorsal striatum. Repeated and challenge administration of KCSCs (nicotine content: 0.4 mg/kg, subcutaneous) increased psychomotor behaviors (ambulatory, rearing, and rotational activities) and time spent in psychoactive behavioral states compared to exposure to nicotine (0.4 mg/kg) alone. The increase in psychomotor behaviors lasted longer when exposed to repeated and challenge administration of KCSCs compared to nicotine alone. In parallel with sustained increase in psychomotor behaviors, repeated administration of KCSCs also caused long-lasting glutamate release in the dorsal striatum compared to nicotine alone. KCSC-induced changes in psychomotor behaviors and glutamate levels in the dorsal striatum were found to be strongly correlated. These findings suggest that non-nicotine alkaloids in commercial cigarette smoke synergistically act with nicotine on nAChRs, thereby upregulating glutamatergic response in the dorsal striatum, which contributes to the hypersensitization of psychomotor behaviors.