PMID- 28861774 OWN - NLM STAT- MEDLINE DCOM- 20180813 LR - 20181113 IS - 1573-6830 (Electronic) IS - 0272-4340 (Linking) VI - 38 IP - 1 DP - 2018 Jan TI - Doxycycline Used for Control of Transgene Expression has its Own Effects on Behaviors and Bcl-xL in the Rat Hippocampus. PG - 281-288 LID - 10.1007/s10571-017-0545-6 [doi] AB - Doxycycline (Dox)-inducible transgenic approach is used to examine the neural mechanisms of anxiety and depression; however, its own effects on related behaviors are not clear. To address this, in the present study, we tested the anxiety- and depression-like behaviors in rats treated with Dox in drinking water (2 mg/ml) in the elevated plus-maze (EPM; on day 5) and forced swim (FST; on day 8) tests, respectively. In addition, the levels of mRNAs and proteins of brain-derived neurotrophic factor (BDNF) and anti-apoptotic protein Bcl-xL in the hippocampus (HIPP) and frontal cortex (FC) were also analyzed. Consumption of Dox for 4 days induced an anxiogenic-like phenotype that was manifested by the decreased percentages of open arm entries and time spent on the open arms of the EPM. After Dox for 7 days, animals demonstrated more active behavior in the FST than control rats as evidenced by the increase in climbing time. When assessed after the FST, expression of Bcl-xL was increased in the hippocampus of Dox-treated animals. Furthermore, hippocampal Bcl-xL content correlated positively with the duration of climbing in the test. This study is the first to find that Dox in treatment regime used to control transgene expression can affect anxiety- and depression-like behaviors in rats. Dox-induced increase in Bcl-xL expression in the hippocampus may be involved in the moderate activation of FST behavior. FAU - Shishkina, G T AU - Shishkina GT AD - Functional Neurogenomics Laboratory, Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk, Russia, 630090. gtshi@bionet.nsc.ru. FAU - Lanshakov, D A AU - Lanshakov DA AD - Functional Neurogenomics Laboratory, Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk, Russia, 630090. FAU - Bannova, A V AU - Bannova AV AD - Functional Neurogenomics Laboratory, Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk, Russia, 630090. FAU - Kalinina, T S AU - Kalinina TS AD - Functional Neurogenomics Laboratory, Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk, Russia, 630090. FAU - Agarina, N P AU - Agarina NP AD - Functional Neurogenomics Laboratory, Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk, Russia, 630090. FAU - Dygalo, N N AU - Dygalo NN AD - Functional Neurogenomics Laboratory, Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk, Russia, 630090. LA - eng GR - 15-04-07855/Russian Foundation for Basic Research/ GR - 0324-2016-0002/Federal Agency of Scientific Organizations program/ PT - Journal Article DEP - 20170831 PL - United States TA - Cell Mol Neurobiol JT - Cellular and molecular neurobiology JID - 8200709 RN - 0 (Anti-Bacterial Agents) RN - 0 (bcl-X Protein) RN - N12000U13O (Doxycycline) SB - IM MH - Animals MH - Anti-Bacterial Agents/pharmacology/toxicity MH - Anxiety/chemically induced/genetics/*metabolism MH - Depression/chemically induced/genetics/*metabolism MH - Doxycycline/*pharmacology/toxicity MH - Gene Expression MH - Hippocampus/drug effects/*metabolism MH - Male MH - Maze Learning/drug effects/physiology MH - Rats MH - Rats, Wistar MH - Stress, Psychological/chemically induced/genetics/metabolism MH - Swimming/physiology MH - Transgenes/drug effects/*physiology MH - bcl-X Protein/*biosynthesis/genetics OTO - NOTNLM OT - Bcl-xL OT - Doxycycline OT - Elevated plus-maze OT - Forced swim test OT - Hippocampus EDAT- 2017/09/02 06:00 MHDA- 2018/08/14 06:00 CRDT- 2017/09/02 06:00 PHST- 2017/03/30 00:00 [received] PHST- 2017/08/29 00:00 [accepted] PHST- 2017/09/02 06:00 [pubmed] PHST- 2018/08/14 06:00 [medline] PHST- 2017/09/02 06:00 [entrez] AID - 10.1007/s10571-017-0545-6 [pii] AID - 10.1007/s10571-017-0545-6 [doi] PST - ppublish SO - Cell Mol Neurobiol. 2018 Jan;38(1):281-288. doi: 10.1007/s10571-017-0545-6. Epub 2017 Aug 31.