Natural and synthetic estrogens specifically alter nicotine demand and cue-induced nicotine seeking in female rats

Ovarian Hormones Regulate Nicotine Consumption and Accumbens Glutamatergic Plasticity in Female Rats

“…These results indicate that precipitous ovarian hormone loss following OVX does not impair acquisition and that conditions which impact consumption are separable from learning mechanisms. Further, our results support those by Flores et al (2016) and our prior study ( Maher et al, 2021 ), such that OVX decreased nicotine consumption in a volitional self-administration paradigm. Interestingly, when OVX females were given E2 supplementation with or without its metabolite, E1, reductions in nicotine consumption did not reverse regardless of the duration of hormone treatment.…”

“…One study found that 4 d of a high dose of 17β-estradiol (E2) administration following ovariectomy (OVX) increased nicotine intake in female rats ( Flores et al, 2016 ). Our results showed that a lower dose E2 supplementation before nicotine self-administration acquisition partially restores OVX-induced suppression of nicotine consumption ( Maher et al, 2021 ). Importantly, nicotine consumption levels only began to dissociate from OVX-vehicle levels after 14 d of daily supplementation with a physiologically relevant, tonically administered dose of E2.…”

“…and xylazine (8 mg/kg, i.m.) and underwent surgical implantation of intravenous jugular catheters ( n = 109) as described in our previous publications ( Gipson et al, 2013a ; Maher et al, 2021 ). Directly following jugular vein catheterization, a portion of animals underwent either OVX ( n = 78) or sham surgery ( n = 31).…”

“…Rats were trained to self-administer either a low (0.02 mg/kg/infusion; experiment 1) or high (0.06 mg/kg/infusion; experiment 2) dose of intravenous nicotine on an FR-1 schedule of reinforcement which was the same schedule used in food training. Two doses of nicotine were tested to determine whether the effects of E2 on nicotine consumption were dose-dependent, as we have previously shown that estrogens can impact consumption outcomes when the dose is manipulated ( Maher et al, 2021 ). Nicotine was delivered over a 5.9-s period following an active lever press.…”

Logical fallacies and misinterpretations that hinder progress in translational addiction neuroscience

“…It should be noted that the logic that longer access to drug selfadministration better models addictive behaviors because of escalations in use is problematic when animals do not always take more drug under an extended access condition than an animal that receives shorter access. An example of this can be found in comparisons between our recently collected nicotine consumption data from short access sessions (2 hr; Maher et al, 2021) versus studies utilizing extended access sessions (23 hr; Harris et al, 2009) which reveal no difference in total drug consumed between these two session durations. Despite that there are examples such as this in the literature supporting similarities in drug intake between different access durations, the hypothesis remains that extended access is a more predictive model in self-administration studies than short access across drug classes, and that these longer durations of access more closely model compulsive drug-taking (e.g., Vendruscolo et al, 2011).…”