PMID- 19303919 OWN - NLM STAT- MEDLINE DCOM- 20090921 LR - 20211020 IS - 1873-7544 (Electronic) IS - 0306-4522 (Print) IS - 0306-4522 (Linking) VI - 161 IP - 1 DP - 2009 Jun 16 TI - Seizure activity involved in the up-regulation of BDNF mRNA expression by activation of central mu opioid receptors. PG - 301-10 LID - 10.1016/j.neuroscience.2009.03.020 [doi] AB - Chemical-induced seizures up-regulated brain-derived neurotrophic factor (BDNF) mRNA expression. Intracerebroventricular (i.c.v.) administration of endogenous opioids preferentially activating mu opioid receptor (MOR) could also increase BDNF mRNA expression. The aim of this study was to determine to what extent i.c.v. administration of synthetic MOR-selective agonists in rats can modulate both seizure activity and up-regulation of BDNF mRNA expression. Effects and potencies of i.c.v. administration of morphine and [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin (DAMGO), were directly investigated by scoring behavioral seizures and measuring BDNF mRNA expression. In addition, effects of the opioid receptor antagonist naloxone and antiepileptic drugs, diazepam, phenobarbital, and valproate, on i.c.v. MOR agonist-induced behavioral seizures and up-regulation of BDNF mRNA expression were determined. A single i.c.v. administration of morphine (10-100 microg) or DAMGO (0.15-1.5 microg) dose-dependently elicited behavioral seizures and increased BDNF mRNA expression in the widespread brain regions. However, s.c. administration of MOR agonists neither produced behavioral seizures nor increased BDNF mRNA expression. Pretreatment with naloxone 1 mg/kg significantly reduced behavioral seizure scores and the up-regulation of BDNF mRNA expression elicited by i.c.v. morphine or DAMGO. Similarly, diazepam 10 mg/kg and phenobarbital 40 mg/kg significantly blocked i.c.v. MOR agonist-induced actions. Pretreatment with valproate 300 mg/kg only attenuated behavioral seizures, but it did not affect morphine-induced increase of BDNF mRNA expression. This study provides supporting evidence that seizure activity plays an important role in the up-regulation of BDNF mRNA expression elicited by central MOR activation and that decreased inhibitory action of GABAergic system through the modulation on GABA receptor synaptic function by central MOR activation is involved in its regulation of BDNF mRNA expression. FAU - Zhang, H N AU - Zhang HN AD - Department of Biomedical Engineering, College of Engineering, 1101 Beal Avenue, University of Michigan, Ann Arbor, MI 48109, USA. FAU - Ko, M C AU - Ko MC LA - eng GR - R01 DA023213/DA/NIDA NIH HHS/United States GR - MH42251/MH/NIMH NIH HHS/United States GR - P01 MH042251/MH/NIMH NIH HHS/United States GR - DA13685/DA/NIDA NIH HHS/United States GR - R01 DA013685/DA/NIDA NIH HHS/United States GR - DA07281/DA/NIDA NIH HHS/United States GR - P50 DA000254/DA/NIDA NIH HHS/United States GR - R01 DA023213-02/DA/NIDA NIH HHS/United States GR - T32 DA007281/DA/NIDA NIH HHS/United States GR - R01 DA013685-01A1/DA/NIDA NIH HHS/United States GR - P50 DA000254-300015/DA/NIDA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20090319 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Anticonvulsants) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Opioid, mu) RN - 100929-53-1 (Enkephalin, Ala(2)-MePhe(4)-Gly(5)-) RN - 36B82AMQ7N (Naloxone) RN - 76I7G6D29C (Morphine) SB - IM MH - Animals MH - Anticonvulsants/pharmacology MH - Brain-Derived Neurotrophic Factor/*biosynthesis/genetics MH - Drug Synergism MH - Enkephalin, Ala(2)-MePhe(4)-Gly(5)-/administration & dosage/pharmacology MH - Injections, Intraventricular MH - Male MH - Morphine/administration & dosage/pharmacology MH - Naloxone/pharmacology MH - RNA, Messenger/*biosynthesis MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Opioid, mu/*agonists/antagonists & inhibitors MH - Seizures/*metabolism/physiopathology MH - Up-Regulation PMC - PMC2680449 MID - NIHMS103727 EDAT- 2009/03/24 09:00 MHDA- 2009/09/22 06:00 PMCR- 2010/06/16 CRDT- 2009/03/24 09:00 PHST- 2008/10/29 00:00 [received] PHST- 2009/03/07 00:00 [revised] PHST- 2009/03/10 00:00 [accepted] PHST- 2009/03/24 09:00 [entrez] PHST- 2009/03/24 09:00 [pubmed] PHST- 2009/09/22 06:00 [medline] PHST- 2010/06/16 00:00 [pmc-release] AID - S0306-4522(09)00373-X [pii] AID - 10.1016/j.neuroscience.2009.03.020 [doi] PST - ppublish SO - Neuroscience. 2009 Jun 16;161(1):301-10. doi: 10.1016/j.neuroscience.2009.03.020. Epub 2009 Mar 19.