Dr. Desai’s Integrative Neurochemistry Laboratory combines cutting-edge neurochemical techniques with behavioral methodologies in to examine how drugs of abuse or environmental stressors alter brain neurochemical mechanisms to cause behavioral abnormalities that are associated with addiction and neuropsychiatric conditions. Based on these insights, Dr. Desai aims to evaluate the utility of novel treatment strategies that may help manage drug abuse and addiction as well as their co-morbidity with neuropsychiatry conditions.
Early research by Dr. Desai showed that behavioral effects of psychomotor stimulants are paralleled by graded increases in brain dopamine (DA) efflux and that the quantitative nature of this relationship is not altered by a history of stimulant exposure. These results have significant implications for current concepts of addiction, particularly in relation to neuroadaptive changes in the dopaminergic system. He and his colleagues have further characterized the association between changes in brain neurochemistry and behavioral actions of stimulants in genetically modified mice with altered neurochemical milieu in targeted brain regions (i.e., nucleus accumbens) in predictable ways. More recently, Dr. Desai has developed methods combining microdialysis with cutting-edge Liquid Chromatography Mass Spectrometry (LC-MS) analysis to map real-time changes in neurochemical signatures (e.g., monoamines, amino acids, metabolites, endocannabinoids) in the brain that may be induced by exposure to drugs of abuse, other environmental stressors, and neuropsychiatric conditions. Dr. Desai and his team are using this approach to chart how stimulants, opioids, and cannabinoids alter neurochemistry in targeted brain regions (e.g., reward circuit) that may play a key role in their abuse-related behavioral effects.
In recent years, Dr. Desai’s research program has expanded to include NASA-funded investigations to delineate the impact of spaceflight stressors (e.g., space radiation, sleep deprivation, social isolation, and microgravity) alone and in combination on neurochemical signatures that may cause neurocognitive deficits. The possibility of acute and long-term CNS damage to humans induced by these spaceflight stressors during deep space travel is the most poorly explored health risk in ground-based studies of space biology. NASA is deeply concerned about the impact of combined exposure to spaceflight stressors on CNS systems that play a key role in operationally-relevant behavioral and neurocognitive function in-flight and as well terrestrial risk of manifesting neurodegenerative conditions when astronauts return to earth. This information gap has significantly hindered NASA’s ability to realistically estimate spaceflight risk to the CNS, and, consequently, impeded the development of future human deep space missions. Research conducted by Dr. Desai and his colleagues aim to provide key information that will allow NASA to accurately predict how exposure to spaceflight hazards during deep space exploration impacts CNS neurobiological function and help facilitate future human deep space travel, i.e., a mission to Mars.
Over the last decade, Dr. Desai and his team has also been engaged in evaluating the potential of new treatment strategies to help manage addiction to various drugs of abuse. For example, work in his laboratory has shown that nicotinic partial agonist’s do not effectively block behavioral effects of nicotinic ligands, suggesting that that these drugs alone probably will not suffice to effectively combat tobacco addiction and that alternative strategies are needed for smoking cessation programs. Along these lines, in collaboration with biopharmaceutical industry, Dr. Desai evaluated the effects of a novel nanoparticle-based anti-nicotine vaccine on the subjective effects of nicotine in nicotine-naïve and nicotine-experienced monkeys. This work demonstrated that an anti-nicotine vaccine can effectively prevent the expression of nicotine’s effects in nicotine-naïve monkeys and produce long-term and substantive reduction in nicotine’s effects in nicotine-experienced monkeys. Collectively, these observations mark a key advance in our understanding of biobehavioral processes involved in tobacco addiction, and as well, in developing effective pharmacological/immunological medication strategies for smoking cessation. Dr. Desai has expanded this line of research to examine the ability of candidate monoclonal antibodies to counter the adverse effects of nicotine and the opioid fentanyl.