Biology subjects

Curran-Alfaro, C. M.

Publications and source records attributed to Curran-Alfaro, C. M..

4 recordsLinked to original sources

bioRxiv2026

Attenuated conditioned taste aversion for sucrose in female mice with a history of chronic low-dose ethanol exposure.

It is becoming increasingly clear that chronic exposure to lower levels of ethanol impact learning and behavior. To determine the impact of chronic low-dose ethanol exposure on sensitivity to changes in stimulus value, a conditioned taste aversion procedure was used. Adult male and female mice underwent a sucrose two bottle-choice drinking paradigm. Each day, mice received an injection of either low-dose ethanol (0.5g/kg) or saline two hours after sucrose access for 20 days. This was followed by a lithium chloride (LiCl)-induced conditioned taste aversion (CTA) paradigm in which 0.15M LiCl or vehicle injection was administered immediately after sucrose consumption for three days. On the fourth day, changes in sucrose consumption were analyzed. Chronic exposure to low-dose ethanol did not affect sucrose consumption in either female of male mice during two-bottle choice. In female mice, a history of chronic low-dose ethanol exposure blocked the development of LiCl-induced CTA. A history of chronic low-dose ethanol did not impact LiCl-induced CTA in male mice as both ethanol-naive and -exposed male mice who underwent LiCl pairing reduced sucrose consumption. This suggests that low-dose ethanol alters aversion-related learning in female mice which may have implication for development of aberrant behavior and risk for alcohol use disorder (AUD).

animal behavior and cognition↗

bioRxiv2026

Chronic neuropathic pain alters reversal learning without generally impacting sucrose self-administration in mice

Chronic pain is associated with neuropsychiatric comorbidities characterized by impairments in cognitive and behavioral flexibility, yet the direct impact of chronic pain on reward-guided behavior remains poorly understood. Here, we investigated how chronic neuropathic pain altered sucrose-reinforced behavior across multiple behavioral assays with distinct cognitive-behavioral demands in male and female mice. Mice underwent spared nerve injury (SNI) or sham surgery and were tested in operant sucrose self-administration, reversal learning, and extinction training. The impact of acute painful stimulation on sucrose seeking was also assessed. SNI produced stable mechanical hypersensitivity without affecting acquisition or extinction of sucrose self-administration, indicating intact baseline acquisition and sucrose seeking. In contrast, chronic neuropathic pain selectively altered behavioral flexibility: SNI females exhibited faster acquisition of reversal learning, while SNI mice as a group showed impaired inhibition of responding on the previously reinforced lever during early reversal. Acute painful stimulation suppressed sucrose seeking in males, but not in females, independent of chronic pain status. At the neural level, painful mechanical stimulation differentially modulated medial prefrontal cortex (mPFC) activity, increasing infralimbic c-Fos expression in SNI mice while decreasing it in sham controls relative to non-stimulated animals. There was no evidence of chronic mPFC hyperactivity as indexed by {Delta}FosB expression. Together, these findings demonstrate that chronic neuropathic pain did not globally disrupt sucrose reward-related behavior, but instead selectively altered behavioral flexibility and pain-reward interactions in a sex-dependent manner, with accompanying alterations in mPFC engagement following aversive stimulation.

animal behavior and cognition↗

bioRxiv2025

Sex Differences in Low-dose Ethanol Effects on Motivated Behavior and Limbic Corticostriatal Activity

Structured abstractO_ST_ABSBackgroundC_ST_ABSEven at lower doses, ethanol exposure impacts both the brain and behavior. Emerging work has shown that chronic exposure to lower doses of ethanol may lead to inflexible behaviors and promote aberrant reward seeking. This study investigated the impact of chronic, low-dose ethanol exposure on neural substrates of reward and on motivated behavior. MethodsAdult C57BL/6J mice were trained to self-administer sucrose. Throughout training, mice received an injection of low-dose ethanol (0.5g/kg) or saline, 1 hour after each session. Mice did not receive ethanol during testing. Mice were then tested in a PR task in which the reward magnitude of reinforcer was reduced (small or large) or increased (small or large). A subset of mice expressed a retrograde tracer in the nucleus accumbens (NAc), and cFos expression within NAc circuits was analyzed following a sucrose self-administration session. ResultsChronic low-dose ethanol exposure altered behavioral responding in female mice following small changes in reward magnitude. Female mice showed divergent response patterns when there was a small reduction in reward magnitude, with greater proportions of ethanol-exposed female mice either increasing or decreasing responding versus controls. Following a small increase, low-dose ethanol female mice significantly increased responding versus controls. Female - but not male - mice exposed to chronic low-dose ethanol shifted behavioral strategy with a reduction in magazine checking behavior. Low-dose ethanol exposure altered cFos expression within the prelimbic cortex and its projections to the NAc during reward seeking. ConclusionsChronic, low-dose ethanol altered behavioral responding and strategy in female mice in response to changes in reward value. Low-dose ethanol exposure impacted cFos induction in prelimbic cortex and its projections to NAc in both female and male mice. Future studies should investigate the consequences of chronic, low-dose ethanol on the brain and behavior to understand what underlying processes drive aberrant reward-seeking behaviors.

animal behavior and cognition↗

bioRxiv2025

Dissociating the incubation of appetitive and consummatory behavior in a model of oral cocaine self-administration

Cocaine use disorder remains a persistent public health dilemma that currently lacks effective treatment strategies. One key impediment to successful treatment outcomes is increased drug craving that occurs over the course of abstinence and subsequent relapse to drug use. This phenomenon, known as the incubation of drug craving, has been modeled extensively in rodent models of intravenous drug self-administration. As commonly implemented, the design of intravenous self-administration preclinical studies precludes disentangling appetitive and consummatory behaviors as drug seeking (appetitive) and taking (consummatory) is simultaneous. Here, we employed a model of oral cocaine self-administration to interrogate the incubation of drug vs nondrug craving, where the route of administration is identical between reinforcers and appetitive and consummatory behaviors are dissociable. Oral self-administration of cocaine produced detectable levels of cocaine and its metabolite, benzoylecgonine, within the blood and brain, and blood and brain levels of both substrates correlated with cocaine consumption. When tested for seeking-(lever pressing) and taking-related (magazine head entries) behavior after 1 or 21 days of forced abstinence from cocaine or saccharin, we observed incubation of lever pressing among cocaine-administering mice and incubation of magazine entries among saccharin-administering mice. These behavioral changes were accompanied by reduced expression of the glial glutamate transporter GLT-1 within the nucleus accumbens (NAc) of cocaine self-administering mice, regardless of abstinence. Altogether, these results underscore the utility of this model of cocaine self-administration, highlight the conserved nature of incubated cocaine seeking across routes of administration, and demonstrate the dissociable neurobehavioral sequelae of the incubation of reward seeking across reinforcer types.

neuroscience↗