Depression and related disorders are a major public health problem, compounded by the fact that at least half of patients are not effectively treated by currently available medications. Among the most commonly prescribed is the class of selective serotonin (5-HT) reuptake inhibitors (SSRIs), which act to inhibit 5-HT transporter (SERT) mediated 5-HT uptake. The increase in extracellular 5-HT that follows is thought to be critical for initiation of the cascade of downstream events needed for therapeutic effects.

The SwRI-developed human head surrogate and its test methodology show great potential for providing insights into injuries resulting from a variety of ballistic threats. With it, designers will be able to craft helmets that offer improved protection for warfighters.

The liver enzyme phenylalanine hydroxylase is responsible for catabolism of excess phenylalanine in the diet. Deficiencies in levels of the enzyme result in the metabolic disorder phenylketonuria, a disease with devastating neurological consequences if untreated, demonstrating the physiological importance of the enzyme. Central to the proper function of phenylalanine hydroxylase is the regulation of the enzyme by its substrates, phenylalanine and tetrahydrobiopterin, and by phosphorylation. Both forms of regulation require the N-terminal ~117 residue regulatory domain.

This new application entitled 'Training in drug abuse research: behavior and neurobiology' requests five years of funding to support a maximum of four postdoctoral fellows per year for interdisciplinary training in drug and alcohol abuse. Fellows primarily engaged in drug and alcohol research take two required courses and attend seminars, journal clubs, an annual retreat, and monthly chalk talks.

Experimental evidence indicates that cannabis or ?9-tetrahydrocannabinol (THC) use precipitates psychotic symptoms and is associated with a greater risk to develop schizophrenia and worsen its outcome. These observations led to the formulation of the cannabinoid hypothesis of schizophrenia, which postulates that over-activity of the brain endocannabinoid system may contribute to the etiology of this pathology. Recent studies, however, have challenged this hypothesis: for example, drugs aimed at blocking cannabinoid CB1 receptor activity have failed as antipsychotics in clinical trials.

The proportion of underrepresented minorities (URMs) earning doctorate degrees in the basic biomedical sciences has increased modestly over the past few decades. Our proposed Program, the South Texas Advanced Research Training Undergraduate Program (START-UP) is a response to a Funding Opportunity Announcement from the Blueprint Program for Enhancing Neuroscience Diversity through Undergraduate Research Education Experiences (BP-ENDURE).

This grant proposes the development of a novel methodology, based on computational approaches and experiments performed under physiological solution conditions, to complement high-resolution methods for the structure determination of biological macromolecules and their assemblies, and the application of this methodology to two relevant cases, Hsp70 and TGFø. Starting with high-resolution structures, the developed software will generate alternative conformations using molecular dynamics. The conformations will be grouped into equivalence classes (ECs).

Impulsivity, an increased tendency to act without thought or deliberation, is common in psychiatric disorders and often is observed in drug abusers. Although impulsivity might be a predisposing trait that contributes to the development of substance abuse, it might also be a result of drug use, thereby promoting ongoing abuse and possibly relapse.

Schizophrenia is a devastating psychiatric condition that affects up to 1% of the US population. During the previous funding period, we reported that a loss of hippocampal interneuron function, recapitulates the hyperdopaminergic state thought to underlie psychosis in patients. In addition, we have recently provided one of the first reports describing the feasibility of interneuron transplants (derived from fetal medial ganglionic eminence) as a novel therapeutic approach for the treatment of schizophrenia.

Cigarette smoking is a leading cause of cancer as well as cardiovascular and respiratory disease and is the leading preventable cause of death in the United States. Many factors contribute to cigarette smoking, including nicotine, other chemicals in tobacco smoke, and conditioned reinforcers. This competing continuation of an R01 proposal focuses on nicotine and nicotinic acetylcholine receptors (nAChR) as critical determinants of smoking behavior and smoking cessation pharmacotherapy.