Biology subjects

Kash, T. L.

Publications and source records attributed to Kash, T. L..

3 recordsLinked to original sources

bioRxiv2018

Chronic inflammatory pain drives alcohol drinking in a sex-dependent manner

Sex differences in chronic pain and alcohol abuse are not well understood. The development of rodent models is imperative for investigating the underlying changes behind these pathological states. However, past attempts have failed to produce drinking outcomes similar to those reported in humans. In the present study, we investigated whether hind paw treatment with the inflammatory agent Complete Freunds Adjuvant (CFA) could generate hyperalgesia and alter alcohol consumption in male and female C57BL/6J mice. CFA treatment led to greater nociceptive sensitivity for both sexes in the Hargreaves test, and increased alcohol drinking for males in a continuous access two-bottle choice (CA2BC) paradigm. Regardless of treatment, female mice exhibited greater alcohol drinking than males. Following a 2-hour terminal drinking session, CFA treatment failed to produce changes in alcohol drinking, blood ethanol concentration (BEC), and plasma corticosterone (CORT) for both sexes. 2-hr alcohol consumption and CORT was higher in females than males, irrespective of CFA treatment. Taken together, these findings have established that male mice are more susceptible to escalations in alcohol drinking when undergoing pain, despite higher levels of total alcohol drinking and CORT in females. Furthermore, the exposure of CFA-treated C57BL/6J mice to the CA2BC drinking paradigm has proven to be a useful model for studying the relationship between chronic pain and alcohol abuse. Future applications of the CFA/CA2BC model should incorporate manipulations of stress signaling and other related biological systems to improve our mechanistic understanding of pain and alcohol interactions.

animal behavior and cognition↗

bioRxiv2018

Predator odor increases glutamatergic synaptic transmission in the prelimbic cortex via corticotropin-releasing factor receptor 1 signaling

The authors have withdrawn their manuscript because the University of North Carolina at Chapel Hill conducted a research misconduct proceeding and concluded that research misconduct occurred involving results presented in this preprint. Hence, the results and conclusions of the preprint article are no longer reliable. The published version of this preprint (Neuropsychopharmacology, doi: 10.1038/s41386-018-0279-2) is being retracted as well. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

neuroscience↗

bioRxiv2017

Fear extinction requires infralimbic cortex projections to the basolateral amygdala

Fear extinction involves the formation of a new memory trace that attenuates fear responses to a conditioned aversive memory, and extinction impairments are implicated in trauma- and stress-related disorders. Previous studies in rodents have found that the infralimbic prefrontal cortex (IL) and its glutamatergic projections to the basolateral amygdala (BLA) and basomedial amygdala (BMA) instruct the formation of fear extinction memories. However, it is unclear whether these pathways are exclusively involved in extinction, or whether other major targets of the IL, such as the nucleus accumbens (NAc) also play a role. To address this outstanding issue, the current study employed a combination of electrophysiological and chemogenetic approaches in mice to interrogate the role of IL-BLA and IL-NAc pathways in extinction. Specifically, we used patch-clamp electrophysiology coupled with retrograde tracing to examine changes in neuronal activity of the IL and prelimbic cortex (PL) projections to both the BLA and NAc following fear extinction. We found that extinction produced a significant increase in the intrinsic excitability of IL-BLA projection neurons, while extinction appeared to reverse fear induced changes in IL-NAc projection neurons. To establish a causal counterpart to these observations, we then used a pathway-specific Designer Receptors Exclusively Activated by Designer Drugs (DREADD) strategy to selectively inhibit PFC-BLA projection neurons during extinction acquisition. Using this approach, we found that DREADD-mediated inhibition of PFC-BLA neurons during extinction acquisition impaired subsequent extinction retrieval. Taken together, our findings provide further evidence for a critical contribution of the IL-BLA neural circuit to fear extinction.

neuroscience↗