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Chronic Intermittent Access to Alcohol Increases Ca v 1.2 in Dopamine Cells of the Substantia Nigra Pars Compacta
Author(s) -
Rodriguez Eric,
Yamamoto Bryan
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.02485
Subject(s) - substantia nigra , pars compacta , ventral tegmental area , dopamine , tyrosine hydroxylase , medicine , endocrinology , methamphetamine , chemistry , dopaminergic
The high comorbidity of alcohol and methamphetamine (Meth) abuse presents unique toxicological endpoints. The serial exposure to chronic alcohol and then a binge model of Meth results in the loss of dopamine cells from the substantia nigra pars compacta (SNpc) with evidence for calcium‐mediated excitotoxicity that is absent with either drug alone. The objective of this study is to localize and quantify the regional distribution of the increases in Ca v 1.2 in the substantia nigra after a chronic alcohol consumption paradigm in Sprague Dawley rats. We hypothesize that increases in Ca v 1.2 will be primarily in the tyrosine hydroxylase (TH)‐positive cells of the SNpc. Male Sprague Dawley rats were subjected to a 2‐bottle choice of water and chronic alcohol (EtOH) consumption model (i.e., 28‐day intermittent/every other day access to 10% EtOH). At 24h after the last day of EtOH consumption, 4% PFA was perfused intracardially, brains cryostat sectioned, and TH and Cav1.2 immunoreactivities of the sections were identified. Fluorescence images of the SNpc and Ventral Tegmental Area (VTA) were captured at 20x magnification and cells that displayed TH and Cav1.2 co‐localized immunoreactivity were hand‐counted by an investigator blinded to the treatments. Cav1.2 was co‐expressed with 43% of TH positive cells in the SNpc and 66% of TH positive cells in the VTA of control water drinking groups. There was a significant increase (39.3 ± 0.5%, p<0.05) in TH‐positive cells with Cav1.2‐positive immunoreactivity in the SNpc of EtOH‐drinking rats when compared to water drinkers. No such effect was identified with TH‐positive cells of the VTA. The total number of TH positive cells did not change in the alcohol drinking group. Western blot analysis of Cav1.2 protein in tissue that contained the SNpc of EtOH‐drinking rats also showed increases in Cav1.2 . The localized increase in TH‐positive cells of the SNpc, and not the VTA suggests a particular sensitivity of this population of cells to the calcium‐mediated events that occurs following the serial exposure to EtOH and Meth.