Alterations in dopamine and serotonin uptake systems in the striatum of the weaver mutant mouse.
In the striatum of the homozygous weaver mutant mouse (wv/wv), dopamine content, uptake and tyrosine hydroxylase activity are decreased compared to wild-type (+/+) mice. In mice heterozygous for the weaver gene (wv/+), these dopaminergic parameters exhibit only minor reductions compared to +/+ mice. The wv/wv striatum has recently been shown to have an increase in serotonin content. In the present study, the serotonin uptake system of the weaver striatum was investigated. Synaptosomal uptake of [3H] serotonin was determined in the dorsal portion of wv/wv and +/+ striatum, and serotonin uptake sites were examined by the binding of [3H] citalopram in the striatum of wv/wv, wv/+ and +/+ mice. The dopamine uptake system was also investigated in all three genotypes via the binding of [3H] mazindol. Synaptosomal uptake of [3H] serotonin was increased by 79% in the dorsal portion of the wv/wv striatum compared to that seen in the +/+ striatum. The binding of [3H] citalopram was increased by 62% in the dorsolateral and by 111% in the dorsomedial portions of the wv/wv striatum compared to +/+. [3H] Citalopram binding in the wv/+ striatum was also higher than +/+, but this increase did not reach statistical significance. Within the wv/wv striatum, [3H] mazindol binding was almost completely absent (88-89% reduction) in the dorsal portion and severely reduced in the other striatal areas. These data support the notion that the dorsal portion of the wv/wv striatum, which has the severest reduction in dopamine uptake, is hyperinnervated by serotonin fibers.
Stotz
E H
EH
Department of Psychiatry (Institute of Psychiatric Research), Indiana University School of Medicine, Indianapolis.
Palacios
J M
JM
Landwehrmeyer
B
B
Norton
J
J
Ghetti
B
B
Simon
J R
JR
Triarhou
L C
LC
D000818:Animals; D001345:Autoradiography; D015283:Citalopram; D004298:Dopamine / Q000378:metabolism*; D005838:Genotype; D066298:In Vitro Techniques; D007700:Kinetics; D008454:Mazindol; D051379:Mice; D008818:Mice, Neurologic Mutants; D017072:Neostriatum / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism
D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D015283:Citalopram; D012701:Serotonin; D008454:Mazindol; D004298:Dopamine