Cigarette Smoke Extract, but Not Electronic Cigarette aerosol Extract, Inhibits Monoamine Oxidase in vitro and Produces Greater acute aversive/anhedonic Effects Than Nicotine alone on Intracranial Self-Stimulation in Rats.

Introduction:
This article presents a study that compares the relative abuse liability of cigarette smoke extract (CS extract) and electronic cigarette aerosol extract (EC extract) to that of nicotine alone using intracranial self-stimulation (ICSS) in rats. The study also examines the effects of formulations on brain monoamine oxidase (MaO) activity in vitro and ex vivo to evaluate the potential role of MaO inhibition in the ICSS study.

Key Points:

* CS extract contained higher levels of several behaviorally active non-nicotine constituents (e.g., MaO inhibitors such as b-carbolines) than EC extract.
* Nicotine alone reduced ICSS thresholds at a moderate nicotine dose, indicating a reinforcement-enhancing effect, and elevated ICSS thresholds at a high nicotine dose, suggesting an aversive/anhedonic effect.
* CS extract elevated ICSS thresholds compared to nicotine alone at high nicotine doses (1.0 and 1.25 mg/kg) and had greater potency at inhibiting MaO-B activity in vitro compared to MaO-a activity.
* EC extract did not inhibit MaO activity in vitro or ex vivo, and its effects on ICSS did not differ from those of nicotine alone.
* The lack of effects of Vuse Solo Original EC extract on MaO activity in vitro contrasts with a report that EC liquid of this same product inhibited MaO in vitro, potentially due to the loss of constituents during aerosolization.
* The study's ICSS data contrast with some studies reporting greater abuse liability for CS extract than nicotine alone on certain measures of i.v. Sa, potentially due to differences in tobacco products, extract preparation procedures, training procedures, and form of response.
* The current CS extract but not nicotine alone inhibited MaO in vitro, and this may be at least partially attributable to the effects of harmane and/or norharmane in CS extract.

Main Message:
The study suggests that the non-nicotine constituents in the present CS extract do not contribute to the greater abuse liability of cigarettes compared to aNDS apparent in humans. Instead, the aversive effects of high nicotine doses in CS extract may limit the abuse liability of cigarettes by enhancing their aversive effects. Studies using self-administration models are needed to examine how such aversive effects might influence the relative consumption of CS and aNDS extracts.

harris aC, Muelken P, alcheva a, Stepanov I, LeSage MG. Cigarette Smoke Extract, but Not Electronic Cigarette aerosol Extract, Inhibits Monoamine Oxidase in vitro and Produces Greater acute aversive/anhedonic Effects Than Nicotine alone on Intracranial Self-Stimulation in Rats. Frontiers in neuroscience. 2022;16:868088. doi:10.3389/fnins.2022.868088