PMID- 23414063 OWN - NLM STAT- MEDLINE DCOM- 20150511 LR - 20220309 IS - 1369-1600 (Electronic) IS - 1355-6215 (Linking) VI - 19 IP - 5 DP - 2014 Sep TI - Brain-derived neurotrophic factor mediates the suppression of alcohol self-administration by memantine. PG - 758-69 LID - 10.1111/adb.12039 [doi] AB - Brain-derived neurotrophic factor (BDNF) within the striatum is part of a homeostatic pathway regulating alcohol consumption. Memantine, a non-competitive antagonist of N-methyl-D-aspartate receptors, induces expression of BDNF in several brain regions including the striatum. We hypothesized that memantine could decrease ethanol (EtOH) consumption via activation of the BNDF signalling pathway. Effects of memantine were evaluated in Long-Evans rats self-administering moderate or high amounts of EtOH 6, 30 and 54 hours after an acute injection (12.5 and 25 mg/kg). Motivation to consume alcohol was investigated through a progressive ratio paradigm. The possible role for BDNF in the memantine effect was tested by blockade of the TrkB receptor using the pharmacological agent K252a and by the BDNF scavenger TrkB-Fc. Candidate genes expression was also assessed by polymerase chain reaction array 4 and 28 hours after memantine injection. We found that memantine decreased EtOH self-administration and motivation to consume EtOH 6 and 30 hours post-injection. In addition, we found that inhibition or blockade of the BDNF signalling pathway prevented the early, but not the delayed decrease in EtOH consumption induced by memantine. Finally, Bdnf expression was differentially regulated between the early and delayed timepoints. These results demonstrate that an acute injection of memantine specifically reduces EtOH self-administration and motivation to consume EtOH for at least 30 hours. Moreover, we showed that BDNF was responsible for the early effect, but that the delayed effect was BDNF-independent. CI - (c) 2013 The Authors, Addiction Biology (c) 2013 Society for the Study of Addiction. FAU - Jeanblanc, Jerome AU - Jeanblanc J AD - Groupe de Recherche sur l'Alcool et les Pharmacodependances - INSERM ERI 24, UFR de Pharmacie, Universite de Picardie Jules Verne, SFR CAP Sante, France. FAU - Coune, Fabien AU - Coune F FAU - Botia, Beatrice AU - Botia B FAU - Naassila, Mickael AU - Naassila M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130216 PL - United States TA - Addict Biol JT - Addiction biology JID - 9604935 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Carbazoles) RN - 0 (Central Nervous System Depressants) RN - 0 (Enzyme Inhibitors) RN - 0 (Excitatory Amino Acid Antagonists) RN - 0 (Indole Alkaloids) RN - 3K9958V90M (Ethanol) RN - 97161-97-2 (staurosporine aglycone) RN - EC 2.7.10.1 (Receptor, trkB) RN - W8O17SJF3T (Memantine) SB - IM MH - Alcohol Drinking/*prevention & control MH - Animals MH - Brain-Derived Neurotrophic Factor/metabolism/*physiology MH - Carbazoles/pharmacology MH - Central Nervous System Depressants/pharmacology MH - Corpus Striatum/drug effects MH - Dose-Response Relationship, Drug MH - Enzyme Inhibitors/pharmacology MH - Ethanol/pharmacology MH - Excitatory Amino Acid Antagonists/administration & dosage/*pharmacology MH - Indole Alkaloids/pharmacology MH - Injections MH - Male MH - Memantine/administration & dosage/*pharmacology MH - Motivation/drug effects MH - Prefrontal Cortex/drug effects MH - Rats, Long-Evans MH - Receptor, trkB/antagonists & inhibitors MH - Self Administration MH - Signal Transduction/drug effects OTO - NOTNLM OT - Alcohol consumption OT - BDNF OT - memantine OT - prefrontal cortex OT - self-administration OT - striatum EDAT- 2013/02/19 06:00 MHDA- 2015/05/12 06:00 CRDT- 2013/02/19 06:00 PHST- 2013/02/19 06:00 [entrez] PHST- 2013/02/19 06:00 [pubmed] PHST- 2015/05/12 06:00 [medline] AID - 10.1111/adb.12039 [doi] PST - ppublish SO - Addict Biol. 2014 Sep;19(5):758-69. doi: 10.1111/adb.12039. Epub 2013 Feb 16.