The synthetically produced predator odor 2,5-dihydro-2,4,5-trimethylthiazoline increases alcohol self-administration and
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ORIGINAL INVESTIGATION
The synthetically produced predator odor 2,5-dihydro-2,4,5-trimethylthiazoline increases alcohol self-administration and alters basolateral amygdala response to alcohol in rats Viren H. Makhijani 1,2 & Janay P. Franklin, 1,2 & Kalynn Van Voorhies 1 & Brayden Fortino 1 & Joyce Besheer 1,2,3 Received: 15 April 2020 / Accepted: 7 September 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Post-traumatic stress disorder (PTSD) is a psychiatric illness that can increase the risk for developing an alcohol use disorder (AUD). While clinical data has been useful in identifying similarities in the neurobiological bases of these disorders, preclinical models are essential for understanding the mechanism(s) by which stressors increase the risk for escalated alcohol consumption. The purpose of these studies was to examine if exposure of male Long-Evans rats to the synthetically derived predator odor 2,5dihydro-2,4,5-trimethylthiazoline (TMT; a component of fox feces) would increase sweetened alcohol self-administration, potentially by facilitating transfer of salience towards cues, and alter neuronal response to alcohol as measured by the immediate early gene c-Fos. In experiment 1, rats exposed to repeated (4×) TMT showed reductions in port entries in Pavlovian conditioned approach and increases in sweetened alcohol self-administration. In experiment 2, rats exposed to repeated TMT showed blunted basolateral amygdala c-Fos response to alcohol. In experiment 3, rats exposed to single, but not repeated TMT, showed increases in sweetened alcohol self-administration, and no change in anxiety-like behavior or hyperarousal. In experiment 4, rats continued to show a significant corticosterone response to TMT after repeated exposures. In summary, exposure of male rats to TMT can cause escalations in sweetened alcohol self-administration and reduction in BLA response to alcohol. These studies outline and utilize a novel preclinical model that can be used to further neurobiological understanding of the emergence of escalated alcohol consumption following stress exposure. Keywords Predator odor . Glucocorticoids . Alcohol . Amygdala . c-Fos . Stress
Introduction Alcohol is the one of the most widely consumed and abused psychoactive substances in the USA, with approximately 56% of adults having drank alcohol in the past month and 6% of adults having an alcohol use disorder (SAMHSA 2018). One
* Joyce Besheer [email protected] 1
Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Thurston-Bowles Building, CB#7178, Chapel Hill, NC 27599, USA
2
Neuroscience Curriculum, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
3
Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
risk factor for development of alcohol use disorder (AUD) is comorbid post-traumatic stress disorder (PTSD), which epidemiological studies have estimated nearly triples the risk of developing AUD (Jacobsen et al. 2001; K
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