Increased alcohol self-administration following repeated Toll-like receptor 3 agonist treatment in male and female rats

Toll-like receptor (TLR) signaling may play an important role in the neuroimmune system's involvement in the development and maintenance of alcohol use disorder (AUD). In the present study we administered the TLR3 agonist poly(I:C) in male and female Long-Evans rats to determine whether TLR3 ag...

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Veröffentlicht in:Pharmacology, biochemistry and behavior biochemistry and behavior, 2022-05, Vol.216, p.173379-173379, Article 173379
Hauptverfasser: Lovelock, Dennis F., Randall, Patrick A., Van Voorhies, Kalynn, Vetreno, Ryan P., Crews, Fulton T., Besheer, Joyce
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container_start_page 173379
container_title Pharmacology, biochemistry and behavior
container_volume 216
creator Lovelock, Dennis F.
Randall, Patrick A.
Van Voorhies, Kalynn
Vetreno, Ryan P.
Crews, Fulton T.
Besheer, Joyce
description Toll-like receptor (TLR) signaling may play an important role in the neuroimmune system's involvement in the development and maintenance of alcohol use disorder (AUD). In the present study we administered the TLR3 agonist poly(I:C) in male and female Long-Evans rats to determine whether TLR3 agonism can increase alcohol consumption on a daily 15% alcohol operant self-administration paradigm. We found few effects when poly(I:C) was given every-other-day at 0.3 or 1.0 mg/kg. However, when 1.0 mg/kg was given on consecutive days, alcohol intake increased in the days following injections specifically in females. In a second experiment, we found that this effect only emerged when rats had a history of multiple poly(I:C) injections. In the final experiment the poly(I:C) dose was increased to 3.0 mg/kg on consecutive days which resulted in significant reductions in alcohol intake on injection days in females that were not accompanied by subsequent increases. The poly(I:C) dose was increased to 9.0 mg/kg for one final pair of injections which led to reductions in intake in both males and females followed by a male specific delayed increase in alcohol intake. Overall, repeated poly(I:C) administration was able to increase subsequent alcohol consumption in both sexes, with females showing an increase at a lower dose than males. These findings support TLR3 agonism in contributing to increased alcohol consumption and add to the body of work identifying the neuroimmune system as a potential therapeutic target for AUD. •TLR3 activation increases alcohol self-administration in male and female rats.•Increases in alcohol intake emerge after a history of repeated poly(I:C) exposure.•Female rats are more behaviorally sensitive to TLR3 activation than males.
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The poly(I:C) dose was increased to 9.0 mg/kg for one final pair of injections which led to reductions in intake in both males and females followed by a male specific delayed increase in alcohol intake. Overall, repeated poly(I:C) administration was able to increase subsequent alcohol consumption in both sexes, with females showing an increase at a lower dose than males. 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ispartof Pharmacology, biochemistry and behavior, 2022-05, Vol.216, p.173379-173379, Article 173379
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subjects Alcohol
Alcohol Drinking - drug therapy
Alcoholism - drug therapy
Animals
Ethanol - pharmacology
Female
Gonadal Steroid Hormones
Male
Neuroimmune
Poly I-C - pharmacology
Poly(I:C)
Rats
Rats, Long-Evans
Self Administration
TLR3
Toll-like receptor 3
Toll-Like Receptor 3 - agonists
title Increased alcohol self-administration following repeated Toll-like receptor 3 agonist treatment in male and female rats
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