Biology subjects

Wheeler, S. R.

Publications and source records attributed to Wheeler, S. R..

3 recordsLinked to original sources

bioRxiv2024

Presence of distinct operant phenotypes and transient withdrawal-induced escalation of operant ethanol intake in female rats

Operant self-administration is frequently used to investigate the neurobiological mechanisms underlying alcohol seeking and drinking and to test the efficacy of drugs under development for the treatment of alcohol use disorder (AUD). Although widely used by the research community, there is a paucity of operant ethanol self-administration studies that include female subjects. The current study characterizes home cage drinking and operant ethanol self-administration in female Sprague Dawley, Long Evans, and Wistar rats. Rats underwent three weeks of intermittent-access two-bottle choice home cage drinking before being trained to lever press for ethanol in standard operant chambers equipped with contact lickometers. After capturing baseline operant performance, rats were chronically exposed to control or ethanol liquid diet using the Lieber-DeCarli method. Operant ethanol self-administration was re-evaluated after chronic liquid diet exposure to determine whether female rats exhibit similar withdrawal-induced escalation of ethanol intake as is regularly observed in male rats. Our findings reveal the presence of three distinct operant phenotypes (Drinker, Responder, Nonresponder), the prevalence of which within each strain is strikingly similar to our previous observations in males. Within a given phenotype, rats of each strain performed similarly during operant testing. Ethanol intake during home cage drinking was unable to predict future operant phenotype. Relative to controls, Drinkers chronically exposed to ethanol liquid diet exhibited a significant, but transient, escalation in consummatory, but not appetitive, responding during acute withdrawal. Collectively, these data closely parallel many of our previous observations in males while also highlighting potential sex differences in drinking strategies following dependence. The presence of the Responder phenotype reinforces the importance of using direct measures of ethanol consumption. Our findings provide new insight into similarities and differences in operant ethanol self-administration between males and females and emphasize the importance of including females in future studies of ethanol drinking and dependence.

neuroscience↗

bioRxiv2024

Chronic ethanol exposure produces long-lasting, subregion-specific physiological adaptations in RMTg-projecting mPFC neurons

Chronic ethanol exposure produces neuroadaptations in the medial prefrontal cortex (mPFC) which facilitate the maladaptive behaviors interfering with recovery from alcohol use disorder. Despite evidence that different cortico-subcortical projections play distinct roles in behavior, few studies have examined the physiological effects of chronic ethanol at the circuit level. The rostromedial tegmental nucleus (RMTg) is a GABAergic midbrain region involved in aversive signaling and is functionally altered by chronic ethanol exposure. Our recent work identified a dense input from the mPFC to the RMTg, yet the effects of chronic ethanol exposure on this circuitry is unknown. In the current study, we examined physiological changes after chronic ethanol exposure in prelimbic (PL) and infralimbic (IL) mPFC neurons projecting to the RMTg. Adult male Long-Evans rats were injected with fluorescent retrobeads into the RMTg and rendered dependent using a 14-day chronic intermittent ethanol (CIE) vapor exposure paradigm. Whole-cell patch-clamp electrophysiological recordings were performed in fluorescently-labeled (RMTg-projecting) and -unlabeled (projection-undefined) layer 5 pyramidal neurons 7-10 days following ethanol exposure. CIE significantly increased intrinsic excitability as well as excitatory and inhibitory synaptic drive in RMTg-projecting IL neurons. In contrast, no lasting changes in excitability were observed in RMTg-projecting PL neurons, although a CIE-induced reduction in excitability was observed in projection-undefined PL neurons. CIE also increased excitatory synaptic drive in RMTg-projecting PL neurons. These data uncover novel subregion- and circuit-specific neuroadaptations in the mPFC following chronic ethanol exposure and reveal that the IL mPFC-RMTg projection is uniquely vulnerable to long-lasting effects of chronic ethanol.

neuroscience↗

bioRxiv2024

Variables affecting acquisition and maintenance of operant ethanol self-administration in male and female Long-Evans rats

AimsThe goal of the present study was to determine the effect of prior experience with ethanol drinking and changes in session duration on the acquisition and maintenance of operant ethanol self-administration. MethodsAdult male and female Long-Evans rats were trained to operantly self-administer ethanol. A subset of male rats underwent intermittent-access two-bottle choice drinking in the home cage prior to operant training. Controls were given access to two bottles of water. Once fully trained in 30-min operant sessions, session duration was reduced to 15 min for all male and female rats. Differences between 30- and 15-min sessions were also assessed in a separate group of male and female rats trained to self-administer sucrose. ResultsNo differences were observed in acquisition rates, the magnitude of responding for ethanol, or total ethanol consumed between male rats allowed to drink ethanol in the home cage and those that remained ethanol naive prior to operant training. A significant decrease in appetitive and consummatory behaviors was observed in males trained to lever press for either ethanol or sucrose. Females exhibited a similar decrease in operant performance for sucrose, but their behavior was largely unchanged in response to changes in session duration when ethanol was the reinforcer. ConclusionsThese data suggest that the use of prior home cage ethanol drinking as an initiation procedure offers little advantage over no initiation procedure at all. Moreover, reducing operant session duration from 30-min to 15-min has the potential to decrease, rather than increase, levels of ethanol intake. Short summaryIntermittent-access two-bottle choice ethanol drinking offers no advantage as an initiation procedure for operant ethanol self-administration over animals that are ethanol-naive prior to training. In addition, shortening the operant session duration does not increase overall intake or promote binge-like patterns of intake for either ethanol or sucrose reinforcer.

neuroscience↗