Neuroactive steroids such as (3α,5α)3-hydroxypregnan-20-one (3α,5α-THP, allopregnanolone) are potent neuromodulators that enhance GABAergic neurotransmission and produce inhibitory neurobehavioral and anti-inflammatory effects. Chronic ethanol (EtOH) consumption reduces 3α,5α-THP levels in human plasma, but has brain region- and species-specific effects on central nervous system levels of 3α,5α-THP.
Cue-induced reinstatement of alcohol-seeking is a hallmark behavioral pathology of addiction. Evidence suggests that reinstatement (e.g., relapse), may be regulated by cell signaling systems that underlie neuroplasticity. A variety of plasticity events require activation of calcium calmodulin-dependent protein kinase II (CaMKII) in components of the reward pathway, such as the nucleus accumbens and amygdala.
Neuroimmune activation is a key feature of the pathologies of numerous psychiatric disorders including alcoholism, depression, and anxiety. Both HMGB1 and IL-1β have been implicated in brain disorders. Previous studies find HMGB1 andIL-1β form heterocomplexes in vitro with enhanced immune responses, lead to our hypothesis that HMGB1 and IL-1β heterocomplexes formed in vivo to contribute to the pathology of alcoholism.
Prenatal exposure to ethanol induces a relative increase in the numbers of pyramidal tract axons relative to the number of corticospinal projection neurons in somatosensory/motor cortices in the adult rat. The present study examines the effects of ethanol on the numbers of axons in the developing caudal pyramidal tract, i.e., corticospinal axons.
Cycles of alcohol and stress are hypothesized to contribute to alcohol use disorders. How this occurs is poorly understood, although both alcohol and stress activate the neuroimmune system – the immune molecules and cells that interact with the nervous system. The effects of alcohol and stress on the neuroimmune system are mediated in part by peripheral signaling molecules.
Neurogenesis in hippocampal dentate gyrus (DG) and subventricular zone (SVZ) matures during adolescence to adult levels. Binge drinking is prevalent in adolescent humans, and could alter brain neurogenesis and maturation in a manner that persists into adulthood. To determine the impact of adolescent binge drinking on adult neurogenesis, Wistar rats received adolescent intermittent ethanol (AIE) exposure (5.0 g/kg/day, i.g., 2 days on/2 days off from postnatal day, P25–P54) and sacrificed on P57 or P95. Neural progenitor cell proliferation, differentiation, survival and maturation using immunohistochemistry was determined in the DG and SVZ.
Prenatal ethanol exposure can produce structural and functional deficits in the brain and result in Fetal Alcohol Spectrum Disorder (FASD). In rodent models acute exposure to a high concentration of alcohol causes increased apoptosis in the developing brain. A single causal molecular switch that signals for this increase in apoptosis has yet to be identified.
The GABAergic neuroactive steroid (3α,5α)-3-hydroxy-pregnan-20-one (3α,5α-THP; allopregnanolone) enhances GABAergic activity and produces subjective effects similar to ethanol (EtOH). The effect of chronic alcohol exposure on 3α,5α-THP concentrations has been studied in mouse, rat, and monkey limbic brain areas.
Fetal alcohol exposure (FAE) alters hippocampal cell numbers in rodents and primates, and this may be due, in part, to a reduction in the number or migration of neuronal progenitor cells. The olfactory bulb exhibits substantial postnatal cellular proliferation and a rapid turnover of newly formed cells in the rostral migratory pathway, while production and migration of postnatal neurons into the dentate gyrus may be more complex.
Serotonergic neurons of the raphe nucleus regulate sleep, mood, endocrine function, and other processes that mature during adolescence. Alcohol abuse and binge drinking are common during human adolescence. We tested the novel hypothesis that adolescent intermittent ethanol exposure would alter the serotonergic system that would persist into adulthood.
Binge drinking during adolescence is a risk factor for neuropsychiatric disorders that can develop later in life. Histone acetylation is an important epigenetic mechanism that contributes to neurodevelopment.
Human studies have established that adolescence is a period of brain maturation that parallels the development of adult behaviors. However, little is known regarding cortical development in the adult rat brain.
The long-term effects of intermittent ethanol exposure during adolescence (AIE) are of intensive interest and investigation. The effects of AIE on learning and memory and the neural functions that drive them are of particular interest as clinical findings suggest enduring deficits in those cognitive domains in humans after ethanol abuse during adolescence.