PMID- 29380665 OWN - NLM STAT- MEDLINE DCOM- 20200804 LR - 20200804 IS - 1814-1412 (Electronic) IS - 1562-2975 (Linking) VI - 20 IP - 7 DP - 2019 Sep TI - Repeated cocaine exposure dysregulates BDNF expression and signaling in the mesocorticolimbic pathway of the adolescent rat. PG - 531-544 LID - 10.1080/15622975.2018.1433328 [doi] AB - Objectives: Long-term abstinence following cocaine exposure up-regulates brain-derived neurotrophic factor (BDNF) expression in the mesocorticolimbic pathway. Given the increased vulnerability to drug abuse typical of adolescence, we hypothesized that changes in BDNF expression may become manifest early after the end of cocaine treatment in the adolescent brain.Methods: Rats received cocaine injections from postnatal day 28 (PND28) to PND42 and the mesocorticolimbic expression of BDNF was measured by real-time PCR and Western blotting at PND43.Results: In the ventral tegmental area, BDNF-tropomyosin receptor kinase B (TrKappaB) expression and phosphorylation are enhanced while the intracellular signaling is unaltered. In the nucleus accumbens (NAc) shell and core, BDNF and its signaling were down-regulated. In the prelimbic (PL) cortex, we found reduced BDNF expression and increased phosphoprylation of TrKappaB, ERK and AKT. In the infralimbic (IL) cortex, increased BDNF expression was coupled with reduced activity and expression of its downstream targets. To evaluate the role of glutamate on BDNF-independent changes, we investigated the expression of the transporter GLT-1 and the activation of the NMDA receptor subunit GluN2B, which were both increased in the PL cortex while reduced in the IL cortex.Conclusions: Our results show that adolescent cocaine exposure modulates BDNF system early after treatment in the mesocorticolimbic pathway, identifying a complex but specific set of changes that could provide clues for treatment. FAU - Caffino, Lucia AU - Caffino L AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. FAU - Giannotti, Giuseppe AU - Giannotti G AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. FAU - Messa, Giulia AU - Messa G AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. FAU - Mottarlini, Francesca AU - Mottarlini F AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. FAU - Fumagalli, Fabio AU - Fumagalli F AD - Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Milan, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180221 PL - England TA - World J Biol Psychiatry JT - The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry JID - 101120023 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 0 (Receptors, Opioid, kappa) RN - I5Y540LHVR (Cocaine) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*genetics MH - Cerebral Cortex/drug effects/*metabolism MH - Cocaine/administration & dosage MH - Cocaine-Related Disorders/*genetics MH - Male MH - Nucleus Accumbens/drug effects/*metabolism MH - Rats MH - Receptors, N-Methyl-D-Aspartate/genetics MH - Receptors, Opioid, kappa/genetics MH - Signal Transduction MH - Substance Withdrawal Syndrome/genetics OTO - NOTNLM OT - BDNF OT - TrKappaB OT - adolescence OT - cocaine OT - prefrontal cortex EDAT- 2018/01/31 06:00 MHDA- 2020/08/05 06:00 CRDT- 2018/01/31 06:00 PHST- 2018/01/31 06:00 [pubmed] PHST- 2020/08/05 06:00 [medline] PHST- 2018/01/31 06:00 [entrez] AID - 10.1080/15622975.2018.1433328 [doi] PST - ppublish SO - World J Biol Psychiatry. 2019 Sep;20(7):531-544. doi: 10.1080/15622975.2018.1433328. Epub 2018 Feb 21.