Date of Award

2024-12-01

Degree Name

Master of Arts

Department

Psychology

Advisor(s)

Laura E. O'Dell

Abstract

Women are more susceptible to the long-term consequences of chronic nicotine exposure, and clinical evidence has shown that abstinence from nicotine exposure produces a withdrawal syndrome that is intensified by estrogen (E2 in rats) and progesterone (PR) in females. The goal of this Masterâ??s thesis was to determine the mechanisms by which E2 and PR promote withdrawal from nicotine vapor inhalation in female rats. Prior work in male rodents has revealed that nicotine withdrawal is modulated in the medial habenula-interpeduncular nucleus (MHb-IPN) pathway. Our hypothesis is that females experience greater inhibition of the IPN via local interneurons that release the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Also, we hypothesize that E2 and PR promote inhibition of the IPN during withdrawal in females. To address our hypotheses, we examined withdrawal-induced changes in the expression of GABAergic genes (Aim 1) and the impact of ovarian hormones on the expression of GABAergic genes (Aim 2) in the IPN of intact and ovariectomized (OVX) female rats. Rats received 14 days of nicotine vapor inhalation. Withdrawal was then precipitated following administration of the nicotinic receptor antagonist mecamylamine (3.0 mg/kg, sc), and the physical signs of withdrawal were assessed for 10 minutes. After testing, vaginal lavage and cytology procedures were conducted to determine the phase of the estrous cycle they were tested in. Gene expression analyses were then performed to evaluate mRNA levels of various markers of GABAergic inhibition and hormones in the IPN. Intact female rats displayed greater physical signs of nicotine withdrawal compared to controls and OVX females. Additionally, we observed a withdrawal-induced increase in GABAergic and hormone receptor gene targets in the IPN of intact females, and these effects were obliterated in OVX females. These results suggest that ovarian hormones promote nicotine withdrawal severity via increasing inhibition of the IPN.

Language

en

Provenance

Recieved from ProQuest

File Size

48 p.

File Format

application/pdf

Rights Holder

Priscilla Giner

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