Biology subjects

Varodayan, F. P.

Publications and source records attributed to Varodayan, F. P..

3 recordsLinked to original sources

bioRxiv2026

Functional remodeling of the parasubthalamic nucleus drives alcohol drinking escalation in dependence

The neurocircuitry changes mediating the development and maintenance of an alcohol use disorder are complex and dynamic. The parasubthalamic nucleus (PSTN), a small nucleus of the posterior lateral hypothalamus best known for suppressing appetite, is interconnected with brain regions disrupted in addiction; yet its potential role in the regulation of alcohol consumption had never been examined. Here we show that the PSTN exerts potent control over alcohol drinking in mice. Remarkably, the influence of endogenous PSTN activity on voluntary alcohol consumption switches from inhibitory to stimulatory upon induction of alcohol dependence. Among PSTN cells, Crh neurons represent a unique subpopulation that promotes alcohol drinking and fires more in dependent mice. Alcohol intake escalation driven by PSTN Crh neurons involves thalamic output and behavioral disinhibition. Based on our results, PSTN Crh neurons could represent a critical node in the brain circuitry overactive in alcohol addiction driven by reward seeking in humans.

neuroscience↗

bioRxiv2024

Voluntary adolescent alcohol exposure does not increase adulthood consumption of alcohol in multiple mouse and rat models

Adolescence is a period of increased risk taking, including increased alcohol and drug use. Multiple clinical studies report a positive relationship between adolescent alcohol consumption and risk of developing an alcohol use disorder (AUD) in adulthood. However, few preclinical studies have attempted to tease apart the biological contributions of adolescent alcohol exposure, independent of other social, environmental, and stress factors, and studies that have been conducted show mixed results. Here we use several adolescent voluntary consumption of alcohol models, conducted across four labs in three institutes and with two rodent species, to investigate the ramifications of adolescent alcohol consumption on adulthood alcohol consumption in controlled, pre-clinical environments. We consistently demonstrate a lack of robust increases in adulthood alcohol consumption. This work highlights that risks seen in both human datasets and other murine drinking models may be due to unique social and environmental factors - some of which may be unique to humans. HIGHLIGHTSO_LIAdolescent drinking-in-the-dark (DID) binge drinking does not increase adulthood consumption in a DID model or a two bottle choice model in male and female SST-Cre:Ai9 mice C_LIO_LIAdolescent pair-housed intermittent access consumption of alcohol does not increase adulthood consumption in an identical adulthood model in male and female C57BL/6J mice C_LIO_LIAdolescent intermittent access to alcohol does not increase adulthood consumption in male and female Wistar or Fischer 344 rats C_LIO_LIThese complementary datasets across murine models, labs and institutions highlight the need to consider human social factors as well as biological factors C_LI

neuroscience↗

bioRxiv2017

Withdrawal-induced escalated oxycodone self-administration is mediated by kappa opioid receptor function

BackgroundPrescription opioid addiction is a significant health problem characterized by compulsive drug seeking, withdrawal and chronic relapse. We investigated the neurobiological consequences of escalation of prescription opioid use using extended access to intravenous oxycodone self-administration in rats.\n\nMethodsMale Wistar rats acquired oxycodone self-administration (0.15 mg/kg/infusion, i.v.) in 1h or 12h access sessions. Electrophysiological and immunohistochemical studies investigated the effects of oxycodone self-administration on kappa opioid receptor (KOR) regulation of GABAergic signaling and dynorphin expression in the central nucleus of the amygdala (CeA).\n\nResultsRats given 12h access to oxycodone for 5 sessions/week (LgA) escalated their responding more than rats given 1h oxycodone (ShA) or 12h saline access. Slowed escalation of responding was found in rats given 12h access for 7 sessions/week (LgA-7day) or rats pretreated with the KOR antagonist nor-binaltorphamine dihydrochloride (norBNI) before LgA (norBNI+LgA). The KOR agonist U-50488 decreased GABA release in CeA neurons of all groups except LgA. norBNI increased GABA release in control group neurons, suggesting tonic KOR activity. This activity was abolished in ShA, norBNI+LgA, and LgA-7day rat neurons, consistent with decreased CeA dynorphin immunoreactivity observed in LgA-7day rats. However, norBNI effects were reversed (decreased CeA GABA release) in LgA rat neurons.\n\nConclusionsThe experience of intermittent extended withdrawal periods accelerates the escalation of oxycodone self-administration and causes greater dysregulation of CeA KOR-mediated GABAergic signaling. A KOR agonist/antagonist switch effect seen with other drugs of abuse was absent, which suggests that oxycodone-induced neuroadaptations may be distinct from those resulting from other drugs of abuse.

neuroscience↗