β-Nicotyrine and e-cigarette abuse liability II: Behavioral economic demand and intracranial self-stimulation in rats

Given the prominence of electronic nicotine delivery systems (ENDS), understanding the product characteristics that underlie ENDS abuse liabilty is a public health research priority. β-Nicotyrine (β-Nic) is a uniquely prevalent constituent (up to 25 % of nicotine [Nic] levels) in ENDS aerosols that may contribute to ENDS abuse liability. Previously, we found clinically relevant concentration of β-Nic doubled the elimination half-life and prolong the interoceptive (discriminative stimulus) properties of Nic in rats, but that it had little or no psychoactive effects itself. The present study used i.v. self-administration (23 hrs/day) and intracranial self-stimulation (ICSS) paradigms to further evaluate if β-Nic alone has abuse liability or if it enhances the abuse liability of Nic.

We examined if β-Nic (> 25 % of Nic levels) substitutes for Nic (0.03mg/kg/inf) during drug self-administration, and whether combinations of Nic and β-Nic alter the acquisition and behavioral economic demand of i.v. Nic. Reinforcement-enhancing and aversive effects of β-Nic alone or in combination with Nic were also evaluated using ICSS.

Moderately high β-Nic doses (0.03 & 0.10mg/kg/inf) increased demand for Nic (0.03mg/kg/inf). β-Nic alone did not maintain self-administration, affect ICSS, or influence the effects of Nic on ICSS.

β-Nic itself does not have abuse potential in either i.v. self-administration or ICSS models, but it does increase the reinforcing efficacy of self-administered Nic. As such, β-Nic may play a role in the abuse liability of ENDS, which has important treatment and regulatory implications.