Challenge exposure to whole cigarette smoke condensate upregulates locomotor sensitization by stimulating?4132 nicotinic acetylcholine receptors in the nucleus accumbens of rats

Nicotine, the primary addictive substance in tobacco, produces the psychomotor, rewarding, and reinforcing effects of tobacco dependence by stimulating nicotinic acetylcholine receptors (nAChRs) in the brain. The present study determined that alpha 4132 nAChRs regulate locomotor sensitization by altering dopamine concentration in the nucleus accumbens (NAc) after systemic challenge exposure to whole cigarette smoke condensate (WCSC). Rats were administered subcutaneous injection of WCSC (0.2 mg/kg nicotine/day) for 7 consecutive days and then reexposed to WCSC after 3 days of withdrawal. Challenge exposure to WCSC significantly increased locomotor activity. This increase was decreased by the subcutaneous injection of the alpha 4132 nAChR antagonist, DH13E (3 mg/ kg), but not by the intraperitoneal injection of the alpha 7 nAChR antagonist, MLA (5 mg/kg). In parallel with a decrease in locomotor activity, blockade of alpha 4132 nAChRs with DH13E decreased dopamine concentration in the NAc which was elevated by challenge exposure to WCSC. These findings suggest that challenge WCSC leads to the expression of locomotor sensitization by elevating dopamine concentration via stimulation of alpha 4132 nAChRs expressed in neurons of the NAc in rats.

Automated summary

Nicotine stimulates nicotinic acetylcholine receptors (nAChRs) in the brain, leading to the psychomotor, rewarding, and reinforcing effects of tobacco dependence. This study found that alpha 4132 nAChRs regulate locomotor sensitization by altering dopamine concentration in the nucleus accumbens (NAc) after exposure to whole cigarette smoke condensate (WCSC). The findings suggest that challenge WCSC increases locomotor sensitization by elevating dopamine concentration through stimulation of alpha 4132 nAChRs expressed in NAc neurons in rats.