The collective effect of non-nicotine constituents on the reinforcing and neuropharmacological effects of comprehensive cigarette smoke and electronic nicotine delivery system (ENDS) aerosol extracts in rats.

Cigarette smoke extract in rats shows stronger reinforcing and receptor effects than nicotine alone, including greater compensatory responding and COX-1/COX-2 inhibition at smoking-relevant concentrations.

• Why it matters: Non-nicotine constituents may shape tobacco use disorder, but few studies have chemically characterized mixed extracts and compared behavioral and neuropharmacological effects across cigarette smoke versus ENDS.
• What they did: Rats self-administered intravenous cigarette smoke (CS) and ENDS aerosol (EA) extracts versus nicotine alone, while nucleus accumbens dopamine release was measured and receptor binding/function was tested in vitro, including nAChRs and other addiction-related targets.
• The result: CS extract shifted nicotine-like dose-response behavior and produced higher compensatory responding than nicotine alone, with lower Q0 for CS (not EA), comparable stress-induced reinstatement, and greater 4β2 nAChR activation plus broad non-nAChR binding and COX-1/COX-2 inhibition; NAc dopamine release did not differ by formulation.

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