Striatal dopamine innervation and receptor density: regional effects of the weaver mutation.

Mice homozygous for the autosomal recessive gene weaver (wv) exhibit a regionally specific depletion of forebrain dopamine (DA). DA is reduced approximately 70% in the dorsal striatum of homozygotes (wv/wv) relative to heterozygous (+/wv) controls while DA content in ventral striatum is relatively unchanged. The goal of the present study was to determine the regional effects of the weaver mutation on striatal DA receptors and DA uptake sites using quantitative autoradiography. Catecholamine histofluorescence was used to examine midbrain DA-containing cell bodies. Compared to behaviorally normal (+/-) littermates, the binding of [3H]spiroperidol to D2 sites was significantly increased in the dorsal but not ventral striatum of wv/wv mice. Binding of the D1 ligand, [3H]SCH23390, was significantly decreased throughout the striatum of wv/wv mice. The binding of [3H]mazindol to DA uptake sites was dramatically reduced in all wv/wv striatal regions except the ventrolateral portion. Compared to +/- littermates, wv/wv mice had far fewer fluorescent cell bodies in the substantia nigra and a less pronounced reduction of ventral tegmental area fluorescent somata. These findings support the hypothesis that heterogeneities exist in the genetic control of the mesotelencephalic DA system. The results underscore the usefulness of the weaver mouse in the study of mesostriatal sub-systems, receptor regulation, and potentially as a model of human neuropathologies that affect distinct populations of cells in the mesotelencephalic system.

Olfactory deprivation increases dopamine D2 receptor density in the rat olfactory bulb.

Unilateral olfactory deprivation during postnatal development results in significant anatomical and neurochemical changes in the deprived olfactory bulb. Perhaps the most dramatic neurochemical change is the loss of dopaminergic expression by neurons of the glomerular region. We describe here the effects of early olfactory deprivation on other elements of the bulb dopaminergic system, namely the dopamine receptors of the olfactory bulb. Rat pups had a single naris occluded on postnatal day 2 (PN2). On PN20 or PN60, animals were sacrificed and the bulbs were examined for catecholamine levels or D2 and D1 dopamine receptor binding. Receptor densities were quantified by in vitro autoradiography using the tritiated antagonists spiperone (D2) and SCH23390 (D1). Dopamine uptake sites were similarly examined using tritiated mazindol. No significant specific labeling of D1 or mazindol sites was observed in the olfactory bulbs of control or experimental animals at either age. Normal animals displayed prominent labeling of D2 sites in the glomerular and nerve layers. After 60 days of deprivation, deprived bulbs exhibited an average increase in D2 receptor density of 32%. As determined by Scatchard analysis, the mean values for Kd and Bmax were 0.134 nM and 293 fmol/mg protein in normal bulbs, and 0.136 nM and 403 fmol/mg protein in deprived bulbs. The results suggest that, as in the neostriatum, dopamine depletion in the olfactory bulb leads to an upregulation of D2 receptor sites. This change may represent an attempt by the system to adapt neurochemically to reduced dopaminergic activity and thereby maintain bulb function.