7,8-dihydroxyflavone enhances cue-conditioned alcohol reinstatement in rats

Hogarth, Samuel J., Djouma, Elvan, and Van Den Buuse, Maarten (2020) 7,8-dihydroxyflavone enhances cue-conditioned alcohol reinstatement in rats. Brain Sciences, 10 (5). 270.

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Abstract

Alcohol use disorder (AUD) is a detrimental disease that develops through chronic ethanol exposure. Reduced brain-derived neurotrophic factor (BDNF) expression has been associated with AUD and alcohol addiction, however the effects of activation of BDNF signalling in the brain on voluntary alcohol intake reinstatement and relapse are unknown. We therefore trained male and female Sprague Dawley rats in operant chambers to self-administer a 10% ethanol solution. Following baseline acquisition and progressive ratio (PR) analysis, rats were split into drug and vehicle groups during alcohol lever extinction. The animals received two weeks of daily IP injection of either the BDNF receptor, TrkB, agonist, 7,8-dihydroxyflavone (7,8-DHF), or vehicle. During acquisition of alcohol self-administration, males had significantly higher absolute numbers of alcohol-paired lever presses and a higher PR breakpoint. However, after adjusting for body weight, the amount of ethanol was not different between the sexes and the PR breakpoint was higher in females than males. Following extinction, alcohol-primed reinstatement in male rats was not altered by pretreatment with 7,8-DHF when adjusted for body weight. In contrast, in female rats, the weight-adjusted potential amount of ethanol, but not absolute numbers of active lever presses, was significantly enhanced by 7,8-DHF treatment during reinstatement. Analysis of spontaneous locomotor activity in automated photocell cages suggested that the effect of 7,8-DHF was not associated with hyperactivity. These results suggest that stimulation of the TrkB receptor may contribute to reward craving and relapse in AUD, particularly in females.

Item ID: 67202
Item Type: Article (Research - C1)
ISSN: 2076-3425
Keywords: Alcohol use disorder, Brain-derived neurotrophic factor (BDNF), Operant self-administration, Reinstatement, Relapse
Copyright Information: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open accessarticle distributed under the terms and conditions of the Creative Commons Attribution(CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Date Deposited: 27 Apr 2021 01:08
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3209 Neurosciences > 320999 Neurosciences not elsewhere classified @ 100%
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