Biology subjects

Arce Soto, N. M.

Publications and source records attributed to Arce Soto, N. M..

3 recordsLinked to original sources

bioRxiv2026

Unpredictable intermittent access exacerbates loss of control over ethanol drinking

BackgroundLoss of control over drinking is a hallmark feature of alcohol use disorder (AUD) that is modeled preclinically through escalation of ethanol consumption and aversion-resistant drinking. Prior work with other reinforcers suggests that within-session unpredictable, intermittent access (uIntA) promotes these phenotypes. However, the effect of uIntA on voluntary ethanol consumption is unknown. MethodsMale and female Long-Evans rats (n=9-10/group) underwent seven weeks of daily voluntary ethanol (20% v/v) drinking sessions under either a continuous access (ContA) or uIntA schedule. Following four weeks of baseline, rats were rendered dependent using a two-week chronic intermittent ethanol vapor exposure procedure. Daily testing was maintained through one week into withdrawal from vapor exposure. On the final day of testing, ethanol was adulterated with quinine (30 mg/L) to assess aversion-resistant drinking. ResultsRats drinking under ContA and uIntA exhibited similar levels of average daily ethanol consumption at baseline. However, uIntA elicited a more robust dependence-induced escalation of ethanol consumption compared to ContA, with uIntA sustaining escalation through early withdrawal. Additionally, while rats with ContA to ethanol remained sensitive to quinine even after chronic ethanol vapor exposure, uIntA promoted aversion-resistant drinking in ethanol dependent rats. ConclusionsThese results demonstrate that, compared to ContA, uIntA maintains ethanol drinking and exacerbates dependence-induced escalation and aversion-resistant ethanol consumption. This work positions uIntA as a powerful tool to assess psychological and neurobiological factors that may underlie loss of control over drinking.

neuroscience↗

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

Modelling alcohol consumption in rodents using two-bottle choice home cage drinking and optional lickometry-based microstructural analysis

Two-bottle choice home cage drinking is one of the most widely used paradigms to study ethanol consumption in rodents. In its simplest form, animals are provided with access to two drinking bottles, one of which contains regular tap water and the other ethanol, for 24 hr/day with daily intake measured via change in bottle weight over the 24 hr period. Consequently, this approach requires no specialized laboratory equipment. While such ease of implementation is likely the greatest contributor to its widespread adoption by preclinical alcohol researchers, the resolution of drinking data acquired using this approach is limited by the number of times the researcher measures bottle weight (e.g., once daily). However, the desire to examine drinking patterns in the context of overall intake, pharmacological interventions, and neuronal manipulations has prompted the development of home cage lickometer systems that can acquire data at the level of individual licks. Although a number of these systems have been developed recently, the open-source system, LIQ HD, has garnered significant attention in the field for its affordability and user friendliness. Although exciting, this system was designed for use in mice. Here, we review appropriate procedures for standard and lickometer-equipped two-bottle choice home cage drinking. We also introduce methods for adapting the LIQ HD system to rats including hardware modifications to accommodate larger cage size and a redesigned 3D printed bottle holder compatible with standard off-the-shelf drinking bottles. Using this approach, researchers can examine daily drinking patterns in addition to levels of intake in many rats in parallel thereby increasing the resolution of acquired data with minimal investment in additional resources. These methods provide researchers with the flexibility to use either standard bottles or a lickometer-equipped apparatus to interrogate the neurobiological mechanisms underlying alcohol drinking depending on their precise experimental needs. SUMMARYThis protocol describes a standard intermittent-access two-bottle choice home cage drinking paradigm to model alcohol consumption in rats. In addition, it provides step-by-step instructions to augment the standard protocol with a DIY lickometer system that enables microstructural analysis of drinking behavior.

neuroscience↗