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.

Contingent and non-contingent recreational-like exposure to ethanol alters BDNF expression and signaling in the cortico-accumbal network differently / A. Orrù, L. Caffino, F. Moro, C. Cassina, G. Giannotti, A. Di Clemente, F. Fumagalli, L. Cervo. - In: PSYCHOPHARMACOLOGY. - ISSN 0033-3158. - 233:17(2016 Sep), pp. 3149-3160.

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

L. Caffino;G. Giannotti;F. Fumagalli;
2016

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.
BDNF; ethanol; medial prefrontal cortex; nucleus accumbens; self-administration; pharmacology
Settore BIO/14 - Farmacologia
set-2016
lug-2016
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/531321
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