Adolescence is a transitional stage marked by continued brain development. This period is accompanied by physical and neurochemical modifications in the shape and function of the hippocampus, prefrontal cortex, and other limbic system structures. Brain maturation during adolescence, which is typically governed by intrinsic factors, can be dramatically altered by environmental influences such as drugs and alcohol. Unlike many other addictive substances, binge drinking is very common and normative among teenagers and young adults. This repeated pattern of excessive alcohol consumption in adolescents has been shown to cause behavioral changes and neurocognitive impairments that include increased anxiety, risky decision-making, and learning deficits, which could lead to the development of alcohol use disorder (AUD). This manuscript highlights factors that lead to adolescent binge drinking, discusses maturational changes that occur in an adolescent’s brain, and then evaluates the effect of adolescent alcohol consumption on brain structure, function, and neurocognitive abilities in both human studies and animal models. The impact of gender/sex and COVID-19 are briefly discussed. Understanding the factors that promote the onset of adolescent binge drinking and its undesirable consequences could serve as a catalyst for developing therapeutic agents that would decrease or eradicate the damaging effects of alcohol on an adolescent brain.
Introduction A wide variety of nicotine concentrations and formulations are available to users of electronic nicotine delivery systems (ENDS). This is increasingly true when considering the many flavors available with ENDS products. To date, there have been few preclinical investigations into the impact of nicotine doses, with and without flavors, on vaping-related behaviors. This present study evaluated how nicotine concentrations relevant to tank-based and pod-based ENDS, with and without flavors, impact reinforcement-related behavior in a mouse model. Methods Adult male and female C57/BL6J mice were used in vapor-inhalation self-administration assays. Mice were assigned e-liquids containing 6 mg/mL or 60 mg/mL nicotine. Additional mice were assigned these nicotine doses with green apple or menthol flavorants. Mice were trained on fixed-ratio 1 (FR1) for ten, two-hour sessions, then five sessions at FR3, three progressive ratio (PR) sessions, and two FR3 sessions. Results We observed male mice exhibited higher reinforcement-related behavior to menthol-flavored 6 mg/mL nicotine when compared to female mice. Males were only observed to have a menthol-induced enhancement of self-administration at 6 mg/mL nicotine and not 60 mg/mL nicotine. However, female mice exhibited significant menthol-induced increases in reinforcement-related behaviors with 60 mg/mL nicotine. Conclusions These data provide evidence that males and females exhibit different dose sensitivities to nicotine. These sex-dependent differences in nicotine sensitivity also indicate that flavor-induced enhancement in nicotine intake is dependent on the different doses for each sex. IMPLICATIONS There has been much discussion recently regarding the impact of flavors on vaping-related behavior. Our current study may support prior investigations that suggest flavors enhance the palatability of nicotine-containing products. However, this current study provides evidence that males and females exhibit different sensitivities to nicotine.
The United States spends billions of dollars to treat chronic wounds each year. Wound healing is complex in nature which involves several intricate multiphase processes that can be delayed for a number of reasons leading to the development of chronic wounds. Wound healing therapies range from topical preparations to surgical repair with treatment options that vary based on other underlying factors like co-infection, age, or co-morbidities such as diabetes. Historically, micelles and liposomes are some of the nanoparticle drug delivery systems explored to treat chronic wounds; however, recent data suggests that dendrimers have shown potential to rival these systems in treating chronic wounds as well as other diseases. This mini review examines advances in dendrimer nanoparticle drug delivery systems to treat chronic wounds.
Uncertainty is a core component of threat and associated learning processes. One methodological factor impacting uncertainty in threat learning paradigms is the threat reinforcement rate, which refers to the proportion of times a cue is reinforced with an aversive stimulus. This study tested the effect of partial vs continuous threat reinforcement on threat / safety discrimination learning, as indexed by skin conductance response (SCR). Using a within-participants design, fifty-nine participants completed a task in which three colored shapes were paired with electric shock at reinforcement schedules of 100% (CS+), 50% (CS+) and 0% (CS-). In addition, the study examined the relationship between the Intolerance of Uncertainty scale (IU) and two subscales – inhibitory and prospective IU – with threat discrimination learning. The data show heightened SCR in the continuous vs partial reinforcement condition to all stimuli, but limited evidence of enhanced discrimination learning. Furthermore, no association was observed between total IU score and threat-safety discrimination. However, using a two-factor model of IU, findings showed higher inhibitory IU and higher prospective IU were associated with diminished and heightened threat discrimination, respectively. These results contribute to a fast-growing literature exploring how the uncertainty inherent to predictors of threat, individual differences in sensitivity to uncertainty, and interactions between these two factors, can shape the acquisition of threat memory.
ID 20494 Poster Board 335For years, prior research has established the scientific premise that the ventral tegmental area (VTA) and the medial habenula (MHb) mediate aspects of nicotine reward, reinforcement, aversion, and intake. To examine how both the VTA and MHb are involved in nicotine reinforcement-related behavior, we used genetically modified mice (males and females) that express fluorescent nAChRs in a mouse model of vapor self-administration. Mice were trained to acquire self-administration on a FR1 and FR3 schedule using nicotine with or without flavors (menthol or green apple). Green apple and menthol enhanced nicotine vapor self-administration in both male and female mice but in a sex-dependent manner (males at 6 mg/mL nicotine and females at 60 mg/mL nicotine). Following vapor self-administration, brain slices containing the VTA and MHb were prepared to examine self-administration-induced changes in baseline firing and intrinsic excitability. To examine intrinsic excitability, we used a current-step protocol to determine rheobase (current necessary to elicit an action potential) and maximum spikes during current steps. We correlated FR3 active nose pokes (mean of 5 FR3 sessions) to electrophysiological measures to examine how neuronal excitability in the VTA and MHb was linked to reinforcement-related behaviors. We observed that intrinsic excitability of VTA dopamine neurons did not correlate to FR3 active nose pokes; but it did correlate to active and inactive nose poke distinction. We observed that the intrinsic excitability of medial MHb neurons correlated inversely to FR3 active nose pokes (high FR3 nose pokes, lower intrinsic excitability). Correlations were consistent between unflavored or flavored nicotine assignments; but menthol and green apple exhibited greater changes in intrinsic excitability of neurons. These data suggest that the MHb may be critical for the magnitude of nicotine intake while VTA dopamine neurons may regulate the learning-related behavior associated with nicotine intake.
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