Methamphetamine-induced Loss Of Striatal Dopamine Innervation In Bdnf Heterozygote Mice Does Not Further Reduce D-3 Receptor Concentrations

Methamphetamine-induced Loss Of Striatal Dopamine Innervation In Bdnf Heterozygote Mice Does Not Further Reduce D-3 Receptor Concentrations

Joyce J N; Renish L; Osredkar T; Walro J M; Kucera J; Dluzen D E

Synapse

2004

2004-04

Depletion of dopamine (DA) reduces D, receptor number, but D-3 receptor expression is also regulated by brain-derived neurotrophic factor (BDNF). We took advantage of transgenic heterozygous BDNF mutant mice (+/-) to determine if reduced BDNF and loss of DA fibers produced by methamphetamine were additive in their impact on D-3 receptor number. We assessed selective markers of the dopaminergic system including caudate-putamen DA concentrations and quantitative autoradiographic measurement of tyrosine hydroxylase (TH) levels, DA transporter (DAT), and DA D-3 receptor binding between vehicle and methamphetamine-treated BDNF +/- and their wildtype (WT) littermate control mice. Caudate-putamen DA concentrations, TH and DAT levels were significantly reduced following methamphetamine treatment in both WT and BDNF +/- mice. The extent of methamphetamine-induced reduction in TH and DAT was greater for the WT than BDNF +/- mice and DAT levels were also decreased to a greater extent in nucleus accumbens of WT as compared to BDNF +/- mice. Lower D-3 receptor existed in caudate-putamen and nucleus accumbens in BDNF +/- mice and these differences were not affected by methamphetamine treatment. Taken together, these results not only substantiate the importance of BDNF in controlling D-3 receptor expression, but also indicate that a methamphetamine-induced depletion of DA fibers fails to produce an additive effect with lowered BDNF for control of D-3 receptor expression. In addition, the reduction of D-3 receptor expression is associated with a decreased neurotoxic response to methamphetamine in BDNF +/- mice. (C) 2004 Wiley-Liss, Inc.

1-methyl-4-phenyl-1; 2; 3; 6-tetrahydropyridine mptp; behavioral; caudate putamen; differential regulation; dopamine; haloperidol treatment; monkey; motor neurons; mutant mice; Neurosciences & Neurology; neurotrophic factor; nucleus accumbens; parkinsons-disease; parkinsons-disease; sensitization; Striatum; substantia-nigra; transporter; tyrosine hydroxylase

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