Biology subjects

Robinson, D. L.

Publications and source records attributed to Robinson, D. L..

4 recordsLinked to original sources

bioRxiv2026

Transcranial alternating current stimulation reverses adolescent alcohol-induced cellular and behavioral deficits.

BACKGROUND: Alcohol is commonly consumed by adolescents in a binge-like pattern that can produce persistent cognitive impairments. Previous work found that adolescent intermittent ethanol (AIE) exposure reduces parvalbumin expressing (PV+) interneurons and increases perineuronal net (PNN) expression in brain regions critical for cognition. Transcranial alternating current stimulation (tACS), a noninvasive neuromodulation technique, has shown promise for treating psychiatric disorders associated with cognitive dysfunction. Here, we examined whether AIE exposure alters PV+ interneurons and PNN expression in the medial prefrontal cortex (mPFC) and impairs cognition, and whether mPFC-targeted gamma tACS can reverse these effects. METHODS: Sprague Dawley rats (N=139, 50% female) underwent AIE or control exposure during adolescence and received Active or Sham mPFC-targeted gamma tACS treatment for three consecutive days in adulthood. Following stimulation, rats either underwent immunohistochemical assessment of PV+ and PNN expression or behavioral testing using the novel object recognition (NOR) task. RESULTS: AIE exposure reduced PV+ cell counts in the prelimbic cortex, an effect that was reversed by active tACS. In contrast, AIE exposure did not alter PNN measures. Interestingly, active tACS affected the prelimbic and infralimbic cortices more than the anterior cingulate cortex. AIE exposure also reduced recognition memory of a novel object, and this deficit was ameliorated by active tACS when assessed one week after stimulation. Additionally, active stimulation decreased anxiety-like behavior in the open-field test. CONCLUSIONS: Together, these results confirm that adolescent alcohol exposure produces lasting cellular and cognitive alterations and supports mPFC-targeted gamma tACS as a potential intervention for alcohol-induced dysfunction.

neuroscience↗

bioRxiv2026

Developmental Alcohol Exposure Alters Domains of Executive Function in Rodents

Both prenatal alcohol exposure (PAE) and adolescent alcohol exposure (AAE) persistently impair executive function in humans and animal models. Executive function encompasses multiple interrelated domains including working memory, inhibitory control, and behavioral flexibility. We hypothesized that a developmental "double hit" of PAE and AAE would produce more severe behavioral deficits associated with these executive domains compared to alcohol-naive and single-exposed animals. We tested this hypothesis in rats by assessing disinhibition (low-light elevated plus maze; LL-EPM), behavioral flexibility (attentional set shift test; ASST), and working memory (spontaneous alternations in a T-maze); we also tested behavioral flexibility (ASST) in mice. Pregnant Sprague Dawley rats received water or 5 g/kg alcohol from gestational day (GD)13.5-GD20.5, and offspring received water or 5 g/kg alcohol on a 2-day-on, 2-day-off paradigm from postnatal day (PD)25 to PD54. Pregnant C57BL/6J mice received water or 4.5 g/kg alcohol from GD13.5-GD17.5, and offspring received water or 4.5 g/kg alcohol on a 2-day-on, 2-day-off paradigm from PD25 to PD42. Offspring underwent behavioral testing in young adulthood. Double hit rats showed more exploration in the LL-EPM than controls and fewer alternations in the T-maze than AAE-only rats, suggesting deficits in disinhibition and spatial working memory, respectively. Double hit rats and mice exhibited more errors and/or more trials to criterion in the ASST, indicative of decreased behavioral flexibility. Overall, double hit animals showed altered performance on tests related to executive function, suggesting that the combined exposure alters executive function in a manner distinct from single-exposure models.

animal behavior and cognition↗

bioRxiv2021

Altered cortico-subcortical network after adolescent alcohol exposure mediates behavioral deficits in flexible decision-making

Behavioral flexibility, the ability to modify behavior according to changing conditions, is essential to optimize decision-making. Deficits in behavioral flexibility that persist into adulthood are one consequence of adolescent alcohol exposure, and another is decreased functional connectivity in brain structures involved in decision-making; however, a link between these two outcomes has not been established. We assessed effects of adolescent alcohol and sex on both Pavlovian and instrumental behaviors and functional connectivity in adult animals to determine associations between behavioral flexibility and resting-state functional connectivity. Alcohol exposure impaired attentional set reversals and decreased functional connectivity among cortical and subcortical regions-of-interest that underlie flexible behavior. Moreover, mediation analyses indicated that adolescent alcohol-induced reductions in functional connectivity within a subnetwork of affected brain regions mediated errors committed during reversal learning. These results provide a novel link between persistent reductions in brain functional connectivity and deficits in behavioral flexibility resulting from adolescent alcohol exposure.

neuroscience↗

bioRxiv2020

Diazepam attenuates the effects of cocaine on locomotion, 50-kHz ultrasonic vocalizations and phasic dopamine release in the nucleus accumbens of rats

Background and PurposeCurrently, no effective drug exists to treat cocaine use disorders, which affect millions of people worldwide. Benzodiazepines are potential therapeutic candidates, as microdialysis and voltammetry studies have shown that they can decrease dopamine release in the nucleus accumbens of rodents. In addition, we have recently shown that diazepam blocks the increase in dopamine release and the affective marker 50-kHz ultrasonic vocalizations (USV) induced by DL-amphetamine in rats. Experimental ApproachHere we tested whether administration of 2.5 mg{middle dot}kg-1 diazepam (i.p.) in adult male Wistar rats could block the effects of 20 mg{middle dot}kg-1 cocaine (i.p.) on electrically evoked phasic dopamine release in the nucleus accumbens measured by fast-scan cyclic voltammetry, as well as 50-kHz USV and locomotor activity. Key ResultsCocaine injection increased evoked dopamine release up to 3-fold within 5 min and the increase was significantly higher than baseline for at least 90 min. The injection of diazepam 15 min later attenuated the cocaine effect by nearly 50% and this attenuation was maintained for at least 30 min. Stimulant drugs, natural rewards and reward predictive cues are known to evoke 50-kHz USV in adult rats. In the present study, cocaine increased the number of 50-kHz USV of the flat, step, trill, and mixed kinds by 12-fold. This effect was at maximum 5 min after cocaine injection, decreased with time and lasted at least 40 min. Diazepam significantly blocked this effect for the entire duration of the session. The distance travelled by control rats during a 40-min session of exploration in an open field was at maximum in the first 5 min and decayed progressively until the end of the session. Cocaine-treated rats travelled significantly longer distances when compared to the control group, while diazepam significantly attenuated cocaine-induced locomotion by up to 50%. Conclusions and implicationThese results suggest that the neurochemical, affective, and stimulant effects of cocaine can be mitigated by diazepam. What is already knownO_LIDiazepam decreases dopamine release in the rodent nucleus accumbens (NAc) and reduces some effects produced by DL-amphetamine. C_LI What this study addsO_LIDiazepam attenuated the increase in phasic dopamine release caused by cocaine. C_LIO_LIDiazepam blocked the effect of cocaine on 50-kHz USV and locomotor activity. C_LI Clinical significanceO_LIThis study demonstrates that diazepam can block specific effects of cocaine that likely contribute to addiction. C_LI

pharmacology and toxicology↗