Contingent and non-contingent recreational-like exposure to ethanol alters BDNF expression and signaling in the cortico-accumbal network differently

Alessandro Orrù, Lucia Caffino, Federico Moro, Chiara Cassina, Giuseppe Giannotti, Angelo Di Clemente, Fabio Fumagalli, Luigi Cervo

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Rationale: 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. Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish
Pages (from-to)3149-3160
JournalPsychopharmacology
Volume233
DOIs
Publication statusPublished - 2016

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Brain-Derived Neurotrophic Factor
Ethanol
Prefrontal Cortex
Nucleus Accumbens
Nerve Growth Factors
Alcoholism
Corpus Striatum
Messenger RNA
Self Administration
Proteins
Brain
Pharmaceutical Preparations

Keywords

  • BDNF
  • Ethanol
  • Medial prefrontal cortex
  • Nucleus accumbens
  • Self-administration

ASJC Scopus subject areas

  • Pharmacology

Cite this

Contingent and non-contingent recreational-like exposure to ethanol alters BDNF expression and signaling in the cortico-accumbal network differently. / Orrù, Alessandro; Caffino, Lucia; Moro, Federico; Cassina, Chiara; Giannotti, Giuseppe; Di Clemente, Angelo; Fumagalli, Fabio; Cervo, Luigi.

In: Psychopharmacology, Vol. 233, 2016, p. 3149-3160.

Research output: Contribution to journalArticle

Orrù, Alessandro ; Caffino, Lucia ; Moro, Federico ; Cassina, Chiara ; Giannotti, Giuseppe ; Di Clemente, Angelo ; Fumagalli, Fabio ; Cervo, Luigi. / Contingent and non-contingent recreational-like exposure to ethanol alters BDNF expression and signaling in the cortico-accumbal network differently. In: Psychopharmacology. 2016 ; Vol. 233. pp. 3149-3160.
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AU - Cassina, Chiara

AU - Giannotti, Giuseppe

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AU - Fumagalli, Fabio

AU - Cervo, Luigi

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N2 - Rationale: 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. Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.

AB - Rationale: 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. Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.

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