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.
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Acknowledgments
We are grateful for financial support (grant EA1034) from ERAB (European Research Advisory Board) and to J.D. Baggott for language editing. AO, ADC, CC, and FM conducted the behavioral experiments. Lucia Caffino, GG, and FF did the molecular analyses. AO, FF, and Luigi Cervo designed the study, did the statistical analyses, interpreted the data, and wrote the manuscript.
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Orrù, A., Caffino, L., Moro, F. et al. Contingent and non-contingent recreational-like exposure to ethanol alters BDNF expression and signaling in the cortico-accumbal network differently. Psychopharmacology 233, 3149–3160 (2016). https://doi.org/10.1007/s00213-016-4358-y
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DOI: https://doi.org/10.1007/s00213-016-4358-y