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Open AccessArticle

7,8-Dihydroxyflavone Enhances Cue-Conditioned Alcohol Reinstatement in Rats

School of Psychology and Public Health, Department of Psychology and Counselling, La Trobe University, Melbourne 3086, VIC, Australia
School of Life Sciences, Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne 3086, VIC, Australia
Department of Pharmacology, University of Melbourne, Melbourne 3010, VIC, Australia
The College of Public Health, Medicinal and Veterinary Sciences, James Cook University Townsville, Townsville 4811, QLD, Australia
Author to whom correspondence should be addressed.
Brain Sci. 2020, 10(5), 270;
Received: 16 April 2020 / Revised: 27 April 2020 / Accepted: 29 April 2020 / Published: 1 May 2020
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. View Full-Text
Keywords: brain-derived neurotrophic factor (BDNF); alcohol use disorder; reinstatement; relapse; operant self-administration brain-derived neurotrophic factor (BDNF); alcohol use disorder; reinstatement; relapse; operant self-administration
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Hogarth, S.J.; Djouma, E.; van den Buuse, M. 7,8-Dihydroxyflavone Enhances Cue-Conditioned Alcohol Reinstatement in Rats. Brain Sci. 2020, 10, 270.

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