Corticostriatal BDNF and alcohol addiction

Abstract

Growth factors, long studied for their involvement in neuronal development and plasticity, also regulate responses to drugs of abuse, including alcohol. This review details the intricate interaction between the Brain-Derived Neurotrophic Factor (BDNF) and alcohol, and provides evidence to suggest that corticostriatal BDNF signaling acts to keep alcohol drinking in moderation. Specifically, we describe studies in rodent models suggesting that moderate consumption of alcohol increases BDNF levels in the dorsal striatum, which in turn act to suppress alcohol intake by activating a Mitogen-Activated Protein Kinase (MAPK)-dependent genomic mechanism. We further provide data to suggest that alcohol intake levels escalate when the endogenous corticostriatal BDNF pathway becomes dysregulated. Finally, we summarize recent studies suggesting that specific microRNAs targeting BDNF mRNA in the medial prefrontal cortex (mPFC) regulate the breakdown of the protective corticostriatal BDNF pathway.

Adolescent THC exposure in female rats leads to cognitive deficits through a mechanism involving chromatin modifications in the prefrontal cortex

“…48 Re cent studies suggest an important protective role of Bdnf in al cohol use disorders 49 or implicate Bdnf in the medial PFC as a negative regulator of cocaineseeking. 50,51 Based on these obser vations, we might speculate that the increase in Bdnf mRNA levels restricted to adult THC exposure could represent a pro tective response.…”

Exercise as a Sex-Specific Treatment for Substance Use Disorder

“…Both exercise and drugs of abuse modify chromatin containing the brain-derived neurotrophic factor (BDNF) gene (83–85). The efficacy of exercise at reducing anxiety and depression is believed to be mediated via Bdnf signaling (6).…”

A Critical Role of Brain-Derived Neurotrophic Factor in Alcohol Consumption

“…The latter has been conceptualized in the field as the “dark side of addiction” (2–5). Several cellular mechanisms involving corticotropin-releasing factor, neuropeptide Y, gamma-aminobutyric, glutamate, and dopaminergic systems within key brain structures have been identified to underlie the neurobiological basis of both positive and negative reinforcement properties of alcohol addiction (2–6). One other cellular molecule appears to be BDNF, and related signaling mechanisms acting within specific brain circuitry regulate synaptic plasticity associated with alcohol drinking behaviors (3–6).…”

“…We now know that BDNF is a crucial brain signaling protein that is integral to many signaling pathways and whose deficiency in key neural circuits is associated with development of psychiatric disorders, including alcoholism (3–7). It is still unclear how and in which cell types BDNF functions in the brain, but available evidence suggests that BDNF via tropomyosin receptor kinase B (trkB) regulates synaptic plasticity via activation of several signaling systems, most prominently mitogen-activated protein (MAP) kinases leading to activation of the gene transcription factor cAMP-responsive element binding (CREB) protein (5,6). BDNF signaling has been implicated in neurogenesis, neuronal differentiation, and maturation (4–7).…”