Biology subjects

Effinger, D. P.

Publications and source records attributed to Effinger, D. P..

3 recordsLinked to original sources

bioRxiv2022

Sex-Specific Changes in Neuronal Activity and Affective Behavior after Chronic Alcohol Consumption in CRF1-cre Transgenic Rats

Alcohol use disorders (AUDs) are characterized by compulsive alcohol use, loss of control over intake, and a negative emotional state during abstinence. While AUDs are associated with both mood and chronic pain disorders, the relationship between these associations remains unclear. Corticotropin releasing factor-1 receptor (CRF1) has been implicated in alcohol (EtOH) use, affective states, and pain sensitivity; often in a sex-dependent manner. Using CRF1-cre transgenic rats, we found no sex differences in basal affective behavior with the exception of mechanical sensitivity, where females were more sensitive to mechanical stimuli. Following baseline testing, rats began EtOH (or water) drinking under intermittent access conditions. Females consumed more alcohol in the first week, but overall EtOH intake was not significantly different between males and females. Following 3-4 weeks of drinking, rats were tested again for negative affect. EtOH drinking decreased mechanical sensitivity, but no other group effects were observed. However, individual EtOH intake was directly correlated with anxiety- and depressive-like behavior in both sexes. Interestingly, EtOH intake inversely correlated with thermal sensitivity in males only. There were no group differences in CRF1+ neuronal activity in either prelimbic or infralimbic cortices, but final session EtOH intake was significantly correlated with activity in CRF1+ neurons in the infralimbic cortex. Together, our results suggest complex interplay between affective state, EtOH drinking, and the role of prefrontal cortex CRF1-containing neurons in mediating these behaviors. Additionally, these results highlight the importance of examining individual differences in AUD-related behaviors. SIGNIFICANCE STATEMENTDespite alcohol use disorders being extremely comorbid with mood and pain disorders, there is still a limited understanding of the interaction and directionality between the them. To investigate this problem, rats were tested for affective behavior before and after being allowed to drink alcohol for 6 weeks. While baseline behavior did not predict subsequent intake, alcohol intake predicted both anxiety- and depressive-like behavior. These findings were accompanied by increased activity of the corticotropin releasing factor 1 containing neurons in the infralimbic region of the prefrontal cortex. Together, these findings reveal a new mechanism for understanding alcohol use.

neuroscience↗

bioRxiv2022

Sex Differences in Central Amygdala Reactivity following Psychedelic Drug Exposure

Psilocybin, and its active metabolite psilocin, have been shown to elicit rapid and long-lasting symptom improvements in a variety of affective psychiatric illnesses. However, the region-specific alterations underlying these therapeutic effects remain relatively unknown. The central amygdala (CeA) is a primary output region within the extended amygdala that is dysregulated in affective psychiatric disorders. Here, we measured CeA activity using the activity marker c-Fos and CeA reactivity using fiber photometry paired with an aversive air-puff stimulus. We found that psilocin administration acutely increased CeA activity in both males and females and increased stimulus specific CeA reactivity in females, but not males. In contrast, psilocin produced time-dependent decreases in reactivity in males, but not females as early as 2-days and lasting to 28-days post administration. We also measured behavioral responses to the air-puff stimulus and found sex-dependent changes in threat responding but not exploratory behavior or general locomotion. Repeated presentations of the auditory component of the air-puff were also performed and sex-specific effects of psilocin on CeA reactivity to the auditory-alone stimulus were also observed. This study provides new evidence that a single dose of psilocin produces sex-specific, time-dependent, and enduring changes in CeA reactivity and behavioral responding to specific components of an aversive stimulus.

neuroscience↗

bioRxiv2021

Reinforcement learning modeling reveals a reward-history-dependent strategy underlying reversal learning in squirrel monkeys

Insight into psychiatric disease and development of therapeutics relies on behavioral tasks that study similar cognitive constructs in multiple species. The reversal learning task is one popular paradigm that probes flexible behavior, aberrations of which are thought to be important in a number of disease states. Despite widespread use, there is a need for a high-throughput primate model that can bridge the genetic, anatomic, and behavioral gap between rodents and humans. Here, we trained squirrel monkeys, a promising preclinical model, on an image-guided deterministic reversal learning task. We found that squirrel monkeys exhibited two key hallmarks of behavior found in other species: integration of reward history over many trials and a side-specific bias. We adapted a reinforcement learning model and demonstrated that it could simulate monkey-like behavior, capture training-related trajectories, and provide insight into the strategies animals employed. These results validate squirrel monkeys as a model in which to study behavioral flexibility.

animal behavior and cognition↗