Impaired synaptic transmission in dorsal dentate gyrus increases impulsive alcohol seeking |
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| Authors: | Maria Nalberczak-Skó ra,Anna Beroun,Edyta Skonieczna,Anna Cał y,Magdalena Zió ł kowska,Roberto Pagano,Pegah Taheri,Katarzyna Kalita,Ahmad Salamian,Kasia Radwanska |
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| Affiliation: | 1.Laboratory of Molecular Basis of Behavior, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Warsaw, Poland ;2.Experimental Psychopathology Lab, Institute of Psychology of Polish Academy of Sciences, Warsaw, Poland ;3.BRAINCITY, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Warsaw, Poland |
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| Abstract: | Both human and animal studies indicate that the dentate gyrus (DG) of the hippocampus is highly exploited by drug and alcohol abuse. Yet, it is poorly understood how DG dysfunction affects addiction-related behaviors. Here, we used an animal model of alcohol use disorder (AUD) in automated IntelliCages and performed local genetic manipulation to investigate how synaptic transmission in the dorsal DG (dDG) affects alcohol-related behaviors. We show that a cue light induces potentiation-like plasticity of dDG synapses in alcohol-naive mice. This process is impaired in mice trained to drink alcohol. Acamprosate (ACA), a drug that reduces alcohol relapse, rescues the impairment of dDG synaptic transmission in alcohol mice. A molecular manipulation that reduces dDG synaptic AMPAR and NMDAR levels increases impulsive alcohol seeking during cue relapse (CR) in alcohol mice but does not affect alcohol reward, motivation or craving. These findings suggest that hindered dDG synaptic transmission specifically underlies impulsive alcohol seeking induced by alcohol cues, a core symptom of AUD.Subject terms: Addiction, Cellular neuroscience |
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