Biology subjects

Kimbrough, A.

Publications and source records attributed to Kimbrough, A..

3 recordsLinked to original sources

bioRxiv2018

Nuclear localization of TORC1 and cellular co-localization of TORC1 and c-Fos in the visceral neuraxis after systemic LiCl injection

Cyclic-AMP response element binding protein (CREB)-mediated gene expression is critical for the processing of visceral information, including learning about visceral stimuli (e.g. conditioned taste aversion). However, CREB requires additional co-factors to induce gene expression, including transducer of regulated CREB-activity (TORC). The nuclear localization of TORC1 has not been examined previously in the visceral neuraxis. c-Fos, a widely-used marker of activity, is induced by visceral stimulation. If CREB-mediated gene transcription is necessary for c-Fos induction in the visceral neuraxis after systemic LiCl injection, then TORC should be active following stimulation, and co-localized with c-Fos in activated neurons. We examined nuclear (activated) TORC1 in the visceral neuraxis at 30, 60, and 180 minutes after LiCl, as compared to c-Fos induction. Consistent with previous studies we found increases in c-Fos 60 min after LiCl in all regions. Nuclear TORC1 was also increased in the area postrema, NTS, and paraventricular nucleus after LiCl. Surprisingly, in the central amygdala, TORC1 was deactivated after LiCl, such that almost all TORC1 was cytoplasmic, whereas control rats had almost all nuclear TORC1. Fluorescent double-labeling of TORC1 and c-Fos after LiCl found that cellular co-localization of c-Fos and TORC1 was very low across the visceral neuraxis. Nuclear TORC1 expression reveals a population of cells in the visceral neuraxis, independent of c-Fos-positive cells, that are regulated by LiCl. TORC1, and in turn CREB-mediated gene transcription, may not be necessary for c-Fos induction in the visceral neuraxis after LiCl.

neuroscience↗

bioRxiv2018

Forty-Eight Hour Conditioning Produces A Robust Long Lasting Flavor Preference In Rats

Conditioned flavor preference (CFP) learning is a form of associative learning in ingestive behavior. CFP Learning can be rapid and produces preferences of varying strengths that can be exceptionally persistent. We sought to establish a method to produce a robust long-lasting CFP in rats. Rats were given 48-h access (conditioning) to a CS+ flavor (grape or cherry 0.05% Kool-Aid, counterbalanced) mixed with 8% glucose and 0.05% saccharin. In order to determine the strength of conditioning rats were given 14 consecutive days of 24-h access to CS+ and CS- flavors mixed only with 0.05% Kool-Aid and 0.05% saccharin (extinction), then further tested 34 days after the last extinction test (48 days post conditioning) for 2 consecutive days with the CS+ and CS-. We found that not only did the learned CFP fail to extinguish over 14 days of testing, but it also persisted for at least 48 days after conditioning. These data provide a method to produce a robust, long lasting and persistent CFP for use in future ingestive behavior research.

neuroscience↗

bioRxiv2017

CRF1 receptor-dependent increases in irritability-like behavior during abstinence from chronic intermittent ethanol vapor exposure

BackgroundIn humans, emotional and physical signs of withdrawal from ethanol are commonly seen. Many of these symptoms, including anxiety-like and depression-like behavior, have been characterized in animal models of ethanol dependence. One issue with several current behavioral tests measuring withdrawal in animal models is they are often not repeatable within subjects over time. Additionally, irritability, one of the most common symptoms of ethanol withdrawal in humans, has not been well characterized in animal models. The corticotropinreleasing factor (CRF)-CRF1 receptor system has been suggested to be critical for the emergence of anxiety-like behavior in ethanol dependence, but the role of this system in irritability-like behavior has not been characterized.\n\nMethodsThe present study compared the effects of chronic intermittent ethanol vapor exposure (CIE)-induced ethanol dependence on irritabilitylike behavior in rats using the bottle-brush test during acute withdrawal and protracted abstinence. Rats were trained to self-administer ethanol in operant chambers and then either left in a nondependent state or made dependent via CIE. Naive, nondependent, and dependent rats were tested for irritability-like behavior in the bottle-brush test 8 h and 2 weeks into abstinence from ethanol. A separate cohort of dependent rats was used to examine the effect of the specific CRF1 receptor antagonist R121919 on irritability-like behavior.\n\nResultsDependent rats exhibited escalated ethanol intake compared with their own pre-CIE baseline and nondependent rats. At both time-points of abstinence, ethanol-dependent rats exhibited increased aggressive-like responses compared with naive and nondependent rats. R121919 blocked the increased irritability-like behavior in dependent rats.\n\nConclusionsThe effect of R121919 to block increased irritability-like behavior suggests that CRF plays an important role in this behavior, similar to other negative emotional withdrawal symptoms. Quantifying and understanding the molecular basis of irritability-like behavior may yield new insights into withdrawal from ethanol and other drugs of abuse.

neuroscience↗