title: Contingent and non-contingent recreational-like exposure to ethanol alters BDNF expression and signaling in the cortico-accumbal network differently.
abstract: Although brain-derived neurotrophic factor (BDNF) is part of a homeostatic pathway involved in the development of alcohol dependence, it is not clear whether this is also true after recreational ethanol consumption.
  
  
  
  We examined BDNF expression and signaling in the cortico-striatal network immediately and 24 h after either a single intravenous (i.v.) ethanol operant self-administration session or the last of 14 sessions.
  
  
  
  To compare contingent and non-contingent ethanol exposure, we incorporated the "yoked control-operant paradigm" in which rats actively taking ethanol (S-Et) were paired with two yoked controls receiving passive infusions of ethanol (Y-Et) or saline.
  
  
  
  A single ethanol exposure transiently reduced BDNF mRNA levels in the medial prefrontal cortex (mPFC) of Y-Et. Immediately after the last of 14 sessions, mRNA and mature BDNF protein levels (mBDNF) were reduced in the mPFC in both S-Et and Y-Et while mBDNF expression was raised in the nucleus accumbens (NAc), suggesting enhanced anterograde transport from the mPFC. Conversely, 24 h later mBDNF expression and signaling were raised in the mPFC and NAc of S-Et rats but reduced in the NAc of Y-Et rats, with concomitant reduction of downstream signaling pathways.
  
  
  
  Our findings indicate that recreational-like i.v. doses of ethanol promote early changes in neurotrophin expression, depending on the length and modality of administration, the brain region investigated, and the presence of the drug. A rapid intervention targeting the BDNF system might be useful to prevent escalation to alcohol abuse.
authors.affiliation: Experimental Psychopharmacology, Department of Neuroscience, IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Via Giuseppe La Masa 19, 20156, Milan, Italy. alessandro.orru@ift.cnr.it.|Institute of Translational Pharmacology (C.N.R.), Parco Scientifico e Tecnologico della Sardegna, Polaris - Edificio 5 - Località, Piscinamanna, 09010, Pula, Cagliari, Italy. alessandro.orru@ift.cnr.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Orrù
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, 20133, Milan, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Caffino
authors.affiliation: Experimental Psychopharmacology, Department of Neuroscience, IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Via Giuseppe La Masa 19, 20156, Milan, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Moro
authors.affiliation: Experimental Psychopharmacology, Department of Neuroscience, IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Via Giuseppe La Masa 19, 20156, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Cassina
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, 20133, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giannotti
authors.affiliation: Experimental Psychopharmacology, Department of Neuroscience, IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Via Giuseppe La Masa 19, 20156, Milan, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Di Clemente
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, 20133, Milan, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Fumagalli
authors.affiliation: Experimental Psychopharmacology, Department of Neuroscience, IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Via Giuseppe La Masa 19, 20156, Milan, Italy. luigi.cervo@marionegri.it.
authors.forename: Luigi
authors.initials: L
authors.lastname: Cervo
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000187:drug effects* / Q000235:genetics; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000494:pharmacology*; D003216:Conditioning, Operant; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012646:Self Administration; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002492:Central Nervous System Depressants; D012333:RNA, Messenger; D000431:Ethanol
keywords: BDNF; Ethanol; Medial prefrontal cortex; Nucleus accumbens; Self-administration