No description available.

No description available.

No description available.

No description available.

Benzodiazepines (BZs) are widely used in the treatment of anxiety and sleep disorders. However, unwanted side effects, such as sedation, motor impairment, and the potential for physical dependence and tolerance, can hinder their use in the clinic. Elucidating the GABAA receptor subtypes underlying these behavioral effects can facilitate the development of an anxiolytic pharmacotherapy with enhanced clinical utility and reduced unwanted side effects. Subtype selective compounds were used to investigate the underlying receptor mechanisms involved in the observable behavioral effects of BZs. In addition, the receptor mechanisms involved in BZ physical dependence and tolerance were also investigated. In addition to observable behavioral effects and motor impairment (MAP and FRR) of BZs, novel categories of observable sedation (sleep posture, moderate sedation, and deep sedation) have been included. Acutely, sleep posture is likely mediated by α2/3GABAA receptors while α1GABA A receptors may mediate deep sedation associated with BZs. The motor impairing effects observed with the MAP and FRR tasks likely involve an interaction of GABAA receptors containing α1, α2, and α3 subunits. The receptor mechanisms underlying tolerance and physical dependence associated with chronic alprazolam administration were investigated. Tolerance developed rapidly to deep sedation, which is likely mediated by α1GABA A receptors, while sleep posture, which is thought to be mediated by α2/3GABAA receptors, persisted throughout chronic treatment. Motor impairment measured by the MAP and FRR tasks also developed tolerance at a similar rate as deep sedation, further suggesting a role for α1GABA A receptors in these behaviors. Substitution tests were conducted to investigate physical dependence and cross-tolerance. Results suggest physical dependence developed following chronic alprazolam treatment. In addition, α1GABAA receptors likely play a role in physical dependence. Withdrawal effects following substitution tests with zolpidem and NEP-581 precluded the determination of cross-tolerance.

Screening for therapeutic compounds and treatments for diseases of the Brain does not only encompass the successful generation of iPS-derived homogenous neural stem cell populations but also the capacity of the differentiation protocol to derive on-demand region-specific cells. Νoggin, a human recombinant protein, has been extensively used in neural induction protocols but its high production costs and batch-to-batch variation have switched the focus to utilizing small molecules that can substitute noggin. Resultantly, the aim of this study was to optimize neuroepithelial stem cell generation in a cost-efficient fashion as well as to evaluate the impact that patterning factors (i.e. small molecules or proteins that enhance the emergence of type-specific neuronal populations) have on the regionality of the neural stem cell population. Findings in this study suggest that DMH1 is indeed a small molecule that can replace noggin in neural induction protocols as previously documented in literature; DMHI appears also to have a ventralizing effect on the generated neural population. / <p>QC 20201013</p>

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No description available.

The ventrolateral hypothalamus in guinea pigs is an area of the brain which contains a high concentration of receptors for estradiol and progesterone. This area is also critical for the induction of female sexual receptivity by estradiol and progesterone. The first experiment presented in this dissertation demonstrated that over 35% of the neurons in the ventrolateral hypothalamus which have estrogen-induced progestin receptors also contain the neuropeptide substance P. The ventrolateral hypothalamus was the primary place in the forebrain where progestin receptors and substance P occurred in the same cells. Thus, the ventrolateral hypothalamus may be an important site in the regulation of substance P by steroid hormones. The second experiment determined the efferent projections from the steroid-sensitive, ventrolateral hypothalamus. Anterograde tract tracing labeled fibers throughout the preoptic area, medial hypothalamus, amygdala, and the dorsal midbrain. The final experiment examined specific efferent projections of ventrolateral hypothalamic neurons which contained progestin receptors and substance P by combining retrograde tract tracing with fluorescent immunocytochemistry. Most of the neurons containing both substance P and progestin receptors projected to the dorsal midbrain. Fewer of these neurons projected to the bed nucleus of the stria terminalis, preoptic area, or medial amygdala. Some of these pathways may be involved in female sexual behavior, as well as other functions which are mediated by steroid hormones and substance P.

Throughout my education I have found that the psychological interventions in use are largely tailored to the masses, and some may be ill suited for those from certain subpopulations such as Autism Spectrum Disorder (ASD) or Asperger's syndrome (AS). I investigated whether there are statistically significant neurological differences between those with high functioning ASD or Asperger's and those without, with the goal of using those differences to propose what aspects might be used to create new psychological interventions more suited to neurodivergent individuals. After a thorough literature search, I found that the areas seeming to be the common denominators marking out those with ASD or Asperger's were the amygdala and orbito frontal cortex and hippocampus. My hypothesis that such neurological differences could be used to infer new psychological interventions for treating depression did not find support. The hope is that this review will nevertheless serve to inspire other researchers to create new interventions.