Neurochemical and Neurostructural Plasticity in Alcoholism

Abstract

The behavioral manifestations of alcoholism are primarily attributable to the numerous and lasting adaptations that occur in the brain as a result of chronic heavy alcohol consumption. As will be reviewed here, these adaptations include alcohol-induced plasticity in chemical neurotransmission, density and morphology of dendritic spines, as well as neurodegeneration and cerebral atrophy. Within the context of these neuroadaptations that have been observed in both human and animal studies, we will discuss how these changes potentially contribute to the cognitive and behavioral dysfunctions that are hallmark features of alcoholism, as well as how they reveal novel potential pharmacological targets for the treatment of this disorder.

The Guanine Nucleotide Exchange Factor (GEF) Asef2 Promotes Dendritic Spine Formation via Rac Activation and Spinophilin-dependent Targeting

“…The proper formation and maintenance of spines is crucial for efficient synaptic signaling. Interestingly, a nucleotide deletion in Asef2 has been linked to autism, and a single-nucleotide polymorphism in Asef2 has been linked to the co-occurrence of alcohol dependence and depression (77,78); these disorders are associated with spine defects (7,79,80). Collectively, our data point to Asef2 as a key signaling protein in regulating the development of dendritic spines and synapses, which is critical for maintaining normal cognitive and behavioral function.…”

HIV-1 Transgenic Female Rat: Synaptodendritic Alterations of Medium Spiny Neurons in the Nucleus Accumbens

“…Indeed, HIV-1 Tg animals are particularly vulnerable to a variety of drugs of abuse including methamphet-amine (Pang et al 2013; Moran et al 2012), nicotine (Vigorito et al 2013) and ethanol (Sakar and Chang 2013), suggesting a commonality of neuropathological impairment across many different drug classes. It is possible that MSNs might be a common neuropathological link in altered responses of the HIV-1 Tg animals to drugs of abuse, as alterations in MSN spines have been found following cocaine/amphetamine exposure (Shen et al 2014; Dumitriu et al 2012) nicotine exposure (Gipson et al 2013) and alcohol (Gass and Olive 2012). Although women with HIV-1+ status may be particularly vulnerable to the effects of substance abuse relative to matched HIV-1- women (Meyer et al 2013), few translational studies have focused exclusively on females.…”

Enhanced functional connectivity and volume between cognitive and reward centers of naïve rodent brain produced by pro-dopaminergic agent KB220Z

“…While these agents have helped a portion of patients over the years, they have not fully prevented drug craving and relapse. The limited success of treating psychoactive substance abuse with current modalities leaves open the need to develop new therapies [ 3 – 6 ].…”