Alprazolam exposure during adolescence induces long-lasting dysregulation in reward sensitivity to morphine and second messenger signaling in the VTA-NAc pathway.

Autor: Cardona-Acosta AM; Department of Psychological and Brain Sciences and Program in Neuroscience, Texas A&M University, College Station, TX, 77843, USA., Sial OK; Department of Neuroscience, The Scripps Research Institute, Jupiter, FL, USA., Parise LF; Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Gnecco T; Department of Psychological and Brain Sciences and Program in Neuroscience, Texas A&M University, College Station, TX, 77843, USA., Enriquez Marti G; Department of Psychological and Brain Sciences and Program in Neuroscience, Texas A&M University, College Station, TX, 77843, USA., Bolaños-Guzmán CA; Department of Psychological and Brain Sciences and Program in Neuroscience, Texas A&M University, College Station, TX, 77843, USA. bolanos@tamu.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Jul 05; Vol. 13 (1), pp. 10872. Date of Electronic Publication: 2023 Jul 05.
DOI: 10.1038/s41598-023-37696-8
Abstrakt: Increased use of benzodiazepines in adolescents have been reported, with alprazolam (ALP) being the most abused. Drug abuse during adolescence can induce changes with lasting consequences. This study investigated the neurobiological consequences of ALP exposure during adolescence in C57BL/6J male mice. Mice received ALP (0, 0.5, 1.0 mg/kg) once/daily (postnatal day 35-49). Changes in responsiveness to morphine (2.5, 5.0 mg/kg), using the conditioned place preference paradigm, were assessed 24-h and 1-month after ALP exposure. In a separate experiment, mice received ALP (0, 0.5 mg/kg) and then sacrificed 24-h or 1-month after treatment to assess levels of extracellular signal regulated kinase 1/2 (ERK1/2) gene expression, protein phosphorylation, and downstream targets (CREB, AKT) within the ventral tegmental area (VTA) and nucleus accumbens (NAc). ALP-pretreated mice developed a strong preference to the compartment(s) paired with a subthreshold dose (2.5 mg/kg) of MOR short-term, and this effect was also present in the 1-month group. Adolescent ALP exposure resulted in dysregulation of ERK-signaling within the VTA-NAc pathway 24-h and 1-month after ALP exposure. Results indicate ALP exposure during adolescence potentiates the rewarding properties of MOR and induces persistent changes in ERK-signaling within the VTA-NAc pathway, a brain circuit highly implicated in the regulation of both drug reward and mood- related behaviors.
(© 2023. The Author(s).)
Databáze: MEDLINE
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