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• W4377029238 abstract "<b>Abstract ID 18359</b> <b>Poster Board 15</b> Chronic use of psychostimulants, such as cocaine and amphetamine, has been linked to numerous adverse health consequences, including cardiovascular complications. An improved understanding of the causes of excessive psychostimulant intake has the potential to facilitate efforts to reduce the consumption of these drugs and improve human health. Both genetic and environmental factors are thought to influence responses to psychostimulants, but the precise genetic alterations that make individuals differentially sensitive to the effects of these drugs have not been completely defined. Psychostimulants are known to increase the extracellular levels of several neurotransmitters, including dopamine and serotonin (5-HT), and thus genetic alterations in either of these neurotransmitter systems could be predicted to lead to aberrant responses to these drugs. Based on the results of published pharmacological studies, we hypothesized that genetic brain 5-HT deficiency would reduce locomotor sensitization to cocaine and amphetamine. To model brain 5-HT deficiency, we used the tryptophan hydroxylase 2 (R439H) knock-in (KI) mouse line, which harbors a partial loss of function mutation in the brain 5-HT synthesis enzyme, tryptophan hydroxylase 2 (Tph2). Homozygous Tph2KI mutant animals (KI mice) have been shown to exhibit 60-80% reductions in the levels of brain 5-HT compared to their wild-type littermates. Our data reveal that brain 5-HT deficiency does not appear to influence locomotor responses to acute or repeated administration of cocaine or amphetamine. However, our preliminary data suggest that low brain 5-HT reduces sensitivity to amphetamine-induced conditioned place preference. Real-time PCR reveals that several psychostimulant-induced changes in gene expression were unaffected by brain 5-HT deficiency, but a significant genotype by drug interaction was observed for one of the candidate genes tested in the nucleus accumbens. This gene, anaplastic lymphoma kinase (Alk), has been previously implicated in cocaine sensitization and was upregulated in wild-type mice, but not KI animals. Overall, these data provide new insight into the importance of brain 5-HT levels in determining some of the behavioral and molecular responses to psychostimulants. This study was supported by a Small Research Grant from the Villanova Insititue for Research and Scholarship to BDS." @default.
• W4377029238 created "2023-05-19" @default.
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• W4377029238 date "2023-05-18" @default.
• W4377029238 modified "2023-09-29" @default.
• W4377029238 title "Genetic Brain Serotonin Deficiency Significantly Impacts a Subset of Behavioral and Molecular Responses to Psychostimulants in Mice" @default.
• W4377029238 doi "https://doi.org/10.1124/jpet.122.183590" @default.
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