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Striatal dopamine output is compromised within +/− BDNF mice
Author(s) -
Dluzen Dean E.,
Anderson Linda I.,
McDermott Janet L.,
Kucera Jan,
Walro Jon M.
Publication year - 2002
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.10027
Subject(s) - endocrinology , medicine , dopaminergic , dopamine , brain derived neurotrophic factor , neurotrophic factors , striatum , microdialysis , chemistry , basal ganglia , psychology , biology , central nervous system , receptor
Abstract We reported previously that mice lacking one brain‐derived neurotrophic factor (BDNF) allele demonstrate elevated striatal dopamine (DA) concentrations but impaired behavioral responses involving the nigrostriatal dopaminergic (NSDA) system. To test the hypothesis that these elevated striatal DA concentrations are associated with perturbed NSDA functioning, we compared striatal DA output between heterozygous mutant (+/−) and wild‐type littermate control (+/+) BDNF mice under conditions of an intact NSDA system, as well as following methamphetamine (MA)‐induced neurotoxicity. Basal DA output from superfused CS tissue fragments did not differ between +/+ and +/− BDNF mice. Potassium (K+) stimulated DA outputs from intact striatal fragments of +/+ mice were significantly greater than that of +/− BDNF mice. Following MA treatment, K+ stimulated DA output of +/+ mice was statistically equivalent to +/− BDNF mice. Striatal DA concentrations of +/− BDNF mice were elevated, albeit not significantly, in both intact and MA‐treated mice relative to +/+ mice. Following MA treatment, striatal DA concentrations were significantly decreased for both genotypes; however, the degree of DA depletion was significantly greater in +/+ mice. Analyzed collectively, these data show the differential effects exerted by a BDNF mutation upon striatal DA concentrations and output. Notably, lower striatal DA concentrations of +/+ vs. +/− BDNF mice can be contrasted with the significantly greater K+ stimulated DA output from the former. This difference was abolished following MA treatment. These results suggest that processes involved with the dynamics of DA release within the NSDA system may be compromised in +/− BDNF mutant mice. Synapse 43:112–117, 2002. © 2001 Wiley‐Liss, Inc.