Nicotine sensitization (part 1): estradiol or tamoxifen is required during the induction phase and not the expression ph
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ORIGINAL INVESTIGATION
Nicotine sensitization (part 1): estradiol or tamoxifen is required during the induction phase and not the expression phase to enable locomotor sensitization to nicotine in female rats Jennet L. Baumbach 1 & Cheryl M. McCormick 1 Received: 29 June 2020 / Accepted: 19 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Rationale Nicotine sensitization involves two functionally distinct phases: induction and expression. Estradiol enhances nicotine sensitization in female rats, but it is not known whether this enhancement is specific to one or both phases. Objectives We investigated the effects of estradiol selectively during the induction and the expression of nicotine sensitization. Methods Ovariectomy (OVX) rats were administered E2 during the induction (2 injection days) and/or the expression phase (9 days later) of nicotine sensitization. The selective estrogen receptor modulator tamoxifen (agonist of ERα and ERß, agonist of the g-coupled estradiol receptor GPER1) also was used to elucidate receptor candidates for the effects of E2 on nicotine sensitization. Results Gonadally intact female rats exhibited expression of nicotine sensitization after a 9-day delay, whereas OVX females did not. Administration of E2 limited to the induction phase of nicotine sensitization rescued expression of nicotine sensitization in OVX females. Tamoxifen during induction did not alter expression of sensitization in gonadally intact female rats, and, like E2, was sufficient to reverse the dampening effects of OVX on expression of sensitization. Conclusions The enhancing effects of E2 on nicotine sensitization occur during the induction phase of nicotine sensitization, although require a delay to produce the effects on locomotor activity to nicotine, and may involve non-canonical estrogen pathways (e.g., activation of GPER1). Keywords Nicotine . Locomotor sensitization . Estradiol . Tamoxifen . GPER1 . Ovariectomy
Introduction More people are addicted to nicotine (the primary reinforcer in tobacco) than to any other drug (https://www.cdc.gov/ tobacco/data_statistics/fact_sheets/fast_facts/index.htm), and tobacco-related diseases remain the world-leading cause of preventable death (WHO 2019). Women escalate from casual to compulsive cigarette smoking more rapidly than do men (Wetter et al. 1999), and are more likely to relapse after a period of abstinence (Perkins and Scott 2008; Pogun et al. 2017), suggesting that women may be especially vulnerable to nicotine addiction. In rodent models, females acquire nicotine self-administration more rapidly than do males, and are
* Cheryl M. McCormick [email protected] 1
Department of Psychology, Centre for Neuroscience, Brock University, 1812 Sir Isaac Brock Way, St. Catharines, Ontario L2S 3A1, Canada
willing to work harder than males for infusions of nicotine (Donny et al. 2000; Lynch 2009; Flores et al. 2016). Greater propensity toward nicotine self-administration in females is linked to the enhancing effects of estradiol (E2) on
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