2026  July 20th

 

Neuroscience: Synthetic coolants boost nicotine’s addictive effects in mice Springer Nature Press Release.

Synthetic cooling agents used in e-cigarettes may enhance nicotine’s addictive properties, according to a study in mice published in Neuropsychopharmacology. The research suggests that the compounds WS-3 and WS-23, designed to replace menthol in e-cigarettes, can amplify nicotine reinforcement and dopamine release in brain regions linked to addiction.

Menthol has been used in tobacco products for its cooling sensation, but regulatory restrictions on menthol in some regions have led some manufacturers to adopt ‘flavourless’ synthetic coolants that mimic its cooling effect. However, little is known about how these substitutes may influence the brain mechanisms underlying nicotine dependence.

Brandon Henderson and colleagues investigated how the synthetic coolants, WS-3 and WS-23, impact the addictive properties of nicotine in young adult male and female mice. Using an e-cigarette vapour self-administration model, they found that mice exposed to nicotine combined with these two coolants showed higher levels of self-administration than those given nicotine alone following five sessions over the course of three weeks. Measurements of brain activity revealed that this combination also increased dopamine release in the nucleus accumbens — a region associated with reward. Additional experiments indicated that the coolants enhanced the excitability of dopamine-producing neurons in the ventral tegmental area and increased the upregulation of nicotinic acetylcholine receptors, both of which are linked to reinforcement behaviour.

The results suggest that synthetic cooling agents are not pharmacologically inert additives but could actively contribute to nicotine’s addictive potential. The authors note that further work will be needed to identify the precise mechanisms involved.

CONTACT

Brandon Henderson (Marshall University, Huntington, WV, USA)

Email: Hendersonbr@marshall.edu 

 

View the related article: Synthetic cooling agents enhance nicotine reinforcement and mesolimbic dopamine signaling

View the related Research Highlights article: Cool but not harmless: synthetic cooling agents enhance nicotine reinforcement via the mesolimbic dopamine system