Sensitivity to the hypnotic effects of ethanol was examined in Sprague-Dawley male and female rats at 16, 26, 36, 46, 56, or 96 days postnatally. Following administration of 3.5, 4.0, 4.5, or 5.0 g/kg of a 17% v/v ethanol solution, sleep times were recorded and blood alcohol levels (BALs) and brain alcohol levels (BrALs) were measured upon awakening. In addition to examining ethanol sleep time during ontogeny, data were used to estimate acute tolerance (indexed by the slope of the linear regressions of waking BALs and BrALs as a function of dose) and initial brain sensitivity to ethanol (indexed by calculating the y-intercept from the linear regression of BrALs as a function of sleep time). The results showed a marked increase in sensitivity to ethanol hypnosis during ontogeny, with young animals exhibiting shorter ethanol-induced sleep times and high waking BALs and BrALs. This ontogenetic increase in ethanol sensitivity was associated with a developmental decline in acute tolerance, with acute tolerance being most pronounced at postnatal day (P) 16 and evident only up to P36. Initial sensitivity conversely increased with age, with P16 pups showing lower initial brain sensitivity to ethanol than at all other ages. Gender differences emerged in adulthood, with males sleeping significantly longer than females at P56 and P96. These findings suggest that the marked insensitivity of young animals to the hypnotic effects of ethanol is related to both pronounced acute tolerance, as well as reduced initial brain sensitivity to ethanol early in life.

Background The brain undergoes major remodeling during adolescence, resulting in improved cognitive control and decision-making, and reduced impulsivity, components of behavior mediated in part by the maturing frontal lobe. Gamma-amino butyric acid (GABA), the main inhibitory neurotransmitter system, also matures during adolescence, with frontal lobe GABA receptors reaching adult levels late in adolescence. Thus, the objective of this study was to characterize in vivo developmental differences in brain GABA levels. Methods Proton magnetic resonance spectroscopy (MRS) was employed at 4 Tesla to acquire metabolite data from the anterior cingulate cortex (ACC) and the parieto-occipital (POC) cortex in adolescents (n=30) and emerging adults (n=20). Results ACC GABA/Cr levels were significantly lower in adolescents relative to emerging adults, whereas no age differences were observed in the POC. Lower ACC GABA/Cr levels were significantly associated with greater impulsivity and worse response inhibition, with relationships being most pronounced for ACC GABA/Cr and No-Go response inhibition in adolescent males. Conclusions These data provide the first human developmental in vivo evidence confirming frontal lobe GABA maturation, which was linked to impulsiveness and cognitive control. These findings suggest that reduced GABA may be an important neurobiological mechanism in the immature adolescent brain, contributing to the reduced, yet rapidly developing, ability to inhibit risky behaviors and to make decisions, which could compromise adolescent health and safety.

Treatment dropout is a problem of great prevalence and stands as an obstacle to recovery in cocaine-dependent (CD) individuals. Treatment attrition in CD individuals may result from impairments in cognitive control, which can be reliably measured by the Stroop color-word interference task. The present analyses contrasted baseline performance on the color-naming, word-reading, and interference subtests of the Stroop task in CD subjects who completed a cocaine treatment trial (completers: N ¼ 50) and those who dropped out of the trial before completion (non-completers: N ¼ 24). A logistic regression analysis was used to predict trial completion using three models with the following variables: the Stroop task subscale scores (Stroop model); the Hamilton depression rating scale (HDRS) scores (HDRS model); and both the Stroop task subscale scores and HDRS scores (Stroop and HDRS model). Each model was able to significantly predict group membership (completers vs non-completers) better than a model based on a simple constant (HDRS model p ¼ 0.02, Stroop model p ¼ 0.006, and Stroop and HDRS model p ¼ 0.003). Models using the Stroop preformed better than the HDRS model. These findings suggest that the Stroop task can be used to identify cocaine-dependent subjects at risk for treatment dropout. The Stroop task is a widely available, reliable, and valid instrument that can be easily employed to identify and tailor interventions of at risk individuals in the hope of improving treatment compliance.