Sex Differences in the Impact of Electronic Nicotine Vapor on Corticotropin-Releasing Factor Receptor 1 Neurons in the Mouse Ventral Tegmental Area
Year: 2023
Type: article
Abstract: Nicotine engages dopamine neurons in the ventral tegmental area (VTA) to encode reward and drive the development of nicotine addiction, however how nicotine selectively alters other VTA populations remains to be determined. Here, we used male and female CRF1-GFP mice and nicotine vapor exposure to examine the effects of nicotine in VTA corticotropin-releasing factor receptor 1 (CRF1) neurons. We use immunohistochemistry and electrophysiology to examine neuronal activity, excitability, and inhibitory signaling. We found that VTA CRF1 neurons are mainly dopaminergic and project to the nucleus accumbens ( VTA-NAc CRF1 neurons). VTA-NAc CRF1 neurons show greater phasic inhibition in naïve females and greater focal nicotine-induced increases in firing in naïve males. Following acute nicotine vapor exposure, phasic inhibition was not altered, but focal nicotine-induced tonic inhibition was enhanced in females and diminished in males. Acute nicotine vapor exposure did not affect firing in VTA-NAc CRF1 neurons, but females showed lower baseline firing and higher focal nicotine-induced firing. Activity (cFos) was increased in the CRF1 dopaminergic VTA population in both sexes, but with greater increases in females. Following chronic nicotine vapor exposure, both sexes displayed reduced basal phasic inhibition and the sex difference in tonic inhibition following acute vapor exposure was no longer observed. Additionally, activity of the CRF1 dopaminergic VTA population was no longer elevated in either sex. These findings reveal sex- and exposure-dependent changes in mesolimbic VTA-NAc CRF1 neuronal activity, inhibitory signaling, and nicotine sensitivity following nicotine vapor exposure. These changes potentially contribute to nicotine-dependent behaviors and the intersection between stress, anxiety, and addiction.
Source: Journal of Neuroscience
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Awards: MOLECULAR AND CELLULAR PATHOGENESIS IN ALCOHOLISM, Impact of electronic nicotine vapor on mouse mesolimbic CRFR1 circuitry and motivated behavior, G2376986389, G290147578, The role of a nucleus tractus solitarius-central amygdala circuit in alcohol-induced plasticity and drinking behavior, Molecular and Circuit Pathogenesis of Alcohol Use Disorders, Neuroscience Predoctoral Training at UNC-Chapel Hill
OpenAlex ID: W4362459024