Here we investigated whether changes in neurogenesis and brain-derived neurotrophic factor (BDNF) expression are possible mechanisms involved in the depression-like symptom during the withdrawal/abstinence period after chronic binge-pattern alcohol consumption given the limited number of studies addressing the link between these factors in the adolescent brain. Forty-seven male Sprague-Dawley rats were used in the study and the experimental protocol started when rats were 25-days old. Rats were assigned to either: (a) ethanol or (b) control group. Animals in each group were further randomized to receive either: BDNF receptor agonist or vehicle. Rats were trained to self-administer ethanol and the binge protocol consisted of daily 30-min experimental sessions 4h into the dark period for 12days. Two days after the last drinking session, rats were tested in the sucrose preference test to evaluate anhedonia and the open field test after habituation to evaluate behavioral despair. Our data showed that: (1) self-administration of alcohol in a binge-like pattern causes inebriation as defined by the National Institute on Alcohol Abuse and Alcoholism and this pattern of alcohol exposure is associated with the development of a depression-like symptom; (2) no significant difference in blood alcohol levels between the two ethanol groups; and (3) chronic binge drinking resulted in the development of a depressive phenotype, decreased survival and neuronal differentiation of neural progenitor cells in the hippocampus, and decreased BDNF effect during the withdrawal period. But the most important finding in our study is that augmenting BDNF actions through the use of tyrosine kinase B (TrkB, a BDNF receptor) agonist restored neurogenesis and abolished the alcohol-induced anhedonia and despair behaviors seen during the withdrawal/abstinence period. Our results suggest that BDNF might be a molecule that can be targeted for interventions in alcoholism-depression co-incidence.
Keywords: 7,8-DHF; 7,8-dihydroflavone; ANOVA; BCA; BDNF; BrdU; Bromodeoxyuridine; DCX; DMSO; EDTA; ELISA; IgG; NIAAA; NPC; National Institute on Alcohol Abuse and Alcoholism; SSC; TBS; TBS-TS; TBS/0.1% Triton X-100/3% donkey serum; Tris-buffered saline; TrkB; analysis of variance; bicinchoninic acid; brain-derived neurotrophic factor; dimethyl sulfoxide; doublecortin; enzyme-linked immunosorbent assay; ethylenediaminetetraacetic acid; hippocampus; i.p.; immunoglobulin G; immunohistochemistry; intraperitoneally; neural progenitor cell; open field test; saline-sodium citrate buffer; sucrose preference test; tyrosine kinase B.
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