PMID- 28624596 OWN - NLM STAT- MEDLINE DCOM- 20180730 LR - 20200106 IS - 2299-5684 (Electronic) IS - 1734-1140 (Linking) VI - 69 IP - 5 DP - 2017 Oct TI - Repeated co-treatment with antidepressants and risperidone increases BDNF mRNA and protein levels in rats. PG - 885-893 LID - S1734-1140(16)30398-X [pii] LID - 10.1016/j.pharep.2017.02.022 [doi] AB - BACKGROUND: Recently, several clinical studies have suggested a beneficial effect of a combination of antidepressants (ADs) with antipsychotic drugs in drug-resistant depression. Moreover, preclinical and clinical studies indicated a role of brain-derived neurotrophic factor (BDNF) in the pathology of depression, as well as in the mechanism of action of ADs. METHODS: In the present study, we investigated the effect of repeated administration of ADs, escitalopram, fluoxetine or mirtazapine and a low dose of risperidone (an atypical antipsychotic drug) given separately or in combination, on the mRNA and protein levels of BDNF or cAMP response element binding (p-CREB) in the hippocampus and frontal cortex of male Wistar rats. ADs were given repeatedly (once daily for 14 days), separately or in combination with a low dose of risperidone. The tissue for biochemical assays was dissected 24h after the last dose of ADs. RESULTS: The obtained results showed that repeated co-treatment with an inactive dose of risperidone and escitalopram or mirtazapine but not fluoxetine increased the BDNF mRNA expression in the hippocampus and frontal cortex. Moreover, combined treatment with an inactive dose risperidone and escitalopram elevated the protein levels of p-CREB in the frontal cortex. While, co-treatment with risperidone and fluoxetine or mirtazapine increased the protein levels of BDNF and p-CREB in both examined regions of the brain. CONCLUSIONS: Our present findings suggest that enhancement levels of BDNF may be essential for the therapeutic effect of co-treatment with ADs and a low dose risperidone in patients with drug-resistant depression. CI - Copyright (c) 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved. FAU - Rogoz, Zofia AU - Rogoz Z AD - Institute of Pharmacology, Polish Academy of Sciences, Department of Pharmacology, Krakow, Poland; The Podhale State Higher Vocational School, Nowy Targ, Poland. Electronic address: rogoz@if-pan.krakow.pl. FAU - Kaminska, Katarzyna AU - Kaminska K AD - Institute of Pharmacology, Polish Academy of Sciences, Department of Pharmacology, Krakow, Poland. FAU - Panczyszyn-Trzewik, Patrycja AU - Panczyszyn-Trzewik P AD - Institute of Pharmacology, Polish Academy of Sciences, Department of Neurobiology, Krakow, Poland. FAU - Sowa-Kucma, Magdalena AU - Sowa-Kucma M AD - Institute of Pharmacology, Polish Academy of Sciences, Department of Neurobiology, Krakow, Poland. LA - eng PT - Journal Article DEP - 20170304 PL - Switzerland TA - Pharmacol Rep JT - Pharmacological reports : PR JID - 101234999 RN - 0 (Antidepressive Agents) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (RNA, Messenger) RN - 0 (Serotonin Antagonists) RN - 01K63SUP8D (Fluoxetine) RN - 0DHU5B8D6V (Citalopram) RN - 250PJI13LM (Mianserin) RN - A051Q2099Q (Mirtazapine) RN - L6UH7ZF8HC (Risperidone) SB - IM MH - Animals MH - Antidepressive Agents/administration & dosage/*pharmacology MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Citalopram/administration & dosage/pharmacology MH - Drug Interactions MH - Fluoxetine/administration & dosage/pharmacology MH - Frontal Lobe/metabolism MH - Gene Expression Regulation/*drug effects MH - Hippocampus/metabolism MH - Mianserin/administration & dosage/analogs & derivatives/pharmacology MH - Mirtazapine MH - RNA, Messenger/genetics/*metabolism MH - Rats MH - Rats, Wistar MH - Risperidone/administration & dosage/*pharmacology MH - Serotonin Antagonists/administration & dosage/*pharmacology OTO - NOTNLM OT - BDNF OT - Escitalopram OT - Fluoxetine OT - Mirtazapine OT - Risperidone EDAT- 2017/06/19 06:00 MHDA- 2018/07/31 06:00 CRDT- 2017/06/19 06:00 PHST- 2016/11/22 00:00 [received] PHST- 2017/02/16 00:00 [revised] PHST- 2017/02/24 00:00 [accepted] PHST- 2017/06/19 06:00 [pubmed] PHST- 2018/07/31 06:00 [medline] PHST- 2017/06/19 06:00 [entrez] AID - S1734-1140(16)30398-X [pii] AID - 10.1016/j.pharep.2017.02.022 [doi] PST - ppublish SO - Pharmacol Rep. 2017 Oct;69(5):885-893. doi: 10.1016/j.pharep.2017.02.022. Epub 2017 Mar 4.