Chronic binge-like alcohol consumption in adolescence causes depression-like symptoms possibly mediated by the effects of BDNF on neurogenesis

Abstract

Here we investigated whether changes in neurogenesis and 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: brain-derived neurotrophic factor (BDNF) receptor agonist or vehicle. Rats were trained to self-administer ethanol and the binge protocol consisted of daily 30-min experimental sessions 4 hours into the dark period for 12 days. 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 (NIAAA) and this pattern of alcohol exposure is associated with the development of depression-like symptom; (2) no significant difference in blood alcohol levels between the 2 ethanol groups; and (3) chronic binge drinking resulted in the development of depressive phenotype, decrease survival and neuronal differentiation of neural progenitor cells in the hippocampus, and decrease 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 receptor 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.

Serum brain-derived neurotrophic factor levels in relation to comorbid depression and cytokine levels in Nepalese men with alcohol-use disorders

“…In our study, we found that both binge-pattern drinkers and more severe AUD patients had a higher mean BDNF level, particularly in those without MD as comorbidity. Studies that show negative associations between binge-pattern drinking and BDNF levels reason higher concordance between binge pattern drinking and depression (Briones & Woods, 2013). However, our sample did not show this relationship.…”

Biochemical and Biophysical Investigation of the Brain-derived Neurotrophic Factor Mimetic 7,8-Dihydroxyflavone in the Binding and Activation of the TrkB Receptor

“…Previously, Segal and co-workers showed that TrkA glycosylation regulates the receptor subcellular localization and activity (55). Although only four N-glycosylation sites are conserved in the Trk family (Asn 26 , Asn 90 , Asn 174 , and Asn 223 ), differences in N-glycosylation may also affect the specificity of ligand-receptor interaction (50). Our observation that neuronal maturation regulates the agonistic effect of 7,8-DHF toward TrkB suggests that TrkB glycosylation might play some role in mediating this event.…”

“…Accordingly, 7,8-DHF rescues synaptic plasticity in aged animals (22)(23)(24). Moreover, 7,8-DHF induces neurogenesis and dampens the development of the "depressive" phenotypes in chronic social defeat and binge-like alcohol consumption mouse models (25,26). Remarkably, 7,8-DHF imitates BDNF and regulates the consolidation of emotional learning (27)(28)(29), rescues the BDNF deficiency-induced learning and memory phenotypes in proprotein convertase PC7 knockout mice (30), and exhibits therapeutic efficacy in a mouse model of Rett syndrome (MeCP2 mutant mice that have reduced levels of BDNF) (31).…”

Decreased rates of operant food self-administration are associated with reward deficits in high-fat feeding mice

“…During testing, mice had the same dietary regime, but they had the option between regular tap water and either sucrose (1 %) or saccharine (0.05 %) solutions, presented in graduated 100-mL glass bottles with a drinking well that extended 4 cm into the cage. Concentrations of sucrose and saccharin were chosen following the ones used by other authors [29][30][31][32]. Bottles were placed symmetrically on the food container, and they were switched every day to avoid position preference.…”