Dopamine D1 and D2 receptors in the forebrain ofDystonia musculorum mutant mice: An autoradiographic survey in relation to dopamine contents

Abstract

Dystonia musculorum (dt(J)/dt(J)) mutant mice suffer from a degeneration of spinocerebellar tracts as well as a dystrophy of peripheral sensory tracts. This neurological mutant has been proposed as an animal model of human cerebellar ataxia, in particular of the Friedreich's type; thus, it was deemed of interest to examine the endogenous contents of dopamine (DA) and metabolites as well as the distribution of DA receptors of the D(1) and D(2) subtypes, in order to delimit the biochemical characteristics of this pathological disorder, and determine an eventual dopaminergic dysfunction in this mutant. Tissue DA and its major metabolites 3, 4-dihydroxyphenylacetic acid, homovanillic acid and 3-methoxytyramine were measured by HPLC coupled to electrochemical detection in six cortical regions, in four divisions of rostral neostriatum and two halves of caudal neostriatum, as well as in olfactory bulb, nucleus accumbens, septum, amygdala, hippocampus, thalamus, hypothalamus, brainstem, cerebellum, substantia nigra, and ventral tegmental area. The only significant difference between dt(J)/dt(J) mice and wild-type controls was an increase in hypothalamic DA contents (+47%). Quantitative autoradiography with [(3)H]SCH23390 and [(3)H]raclopride, to label D(1) and D(2) receptors, respectively, revealed only moderate changes in receptor densities in a few localized regions. In dt(J)/dt(J) mutants, D(1) receptor numbers were found to be higher in thalamus (+27%) as well as in the medio-dorsal (+16%) and in the latero-dorsal (+16%) quadrants of rostral neostriatum, while D(2) receptor densities were greater in the medio-ventral (+32%) and the latero-dorsal (+17%) quadrants. The present results indicate an overall conservation of dopaminergic functions, albeit the few localized sites of increased D(1) and D(2) receptor densities, and that are seemingly independent of the DA innervation pattern, as revealed by the tissue measurements of DA and metabolites. They also rule out a major pathology linked to deficits in DA neurotransmission, and validate this mutant as an animal model of human cerebellar ataxia, probably of the Friedreich type.

Methamphetamine-induced changes in the striatal dopamine pathway in μ-opioid receptor knockout mice

“…Briefly, brain sections were pre-incubated at 4°C for 30 min in a 50 mM Tris-HCI buffer (pH 7.4) containing 120 mM NaCl, 5 mM KCl, 2 mM CaCl 2 , and 1 mM MgCl 2 , and then incubated for 60 min with 1.6 nM of the labeled dopamine D1 receptor antagonist [ 3 H]SCH23390 at room temperature. Other sections were incubated with 30 μM of the dopamine D1 receptor ligand (±)SKF38393 [33] to control for nonspecific binding. The labeled brain sections as well as a set of [ 3 H]-impregnated plastic standards ([ 3 H]Microscale, Amersham Life Science) were placed on Kodak BioMax MS film for 3 weeks (-80°C).…”

Bromocriptine Administration Reduces Hyperphagia and Adiposity and Differentially Affects Dopamine D2 Receptor and Transporter Binding in Leptin-Receptor-Deficient Zucker Rats and Rats with Diet-Induced Obesity

“…D2R binding was measured by quantitative autoradiography in all rats according to well-established procedures [30,31] . To quantify D2R binding, brain sections were preincubated at 4 ° C for 30 min in 50 m M Tris-HCl buffer (pH 7.4) containing 60 m M NaCl and 5 m M KCl, and then incubated for 120 min in the same buffer with (250 Ci) 2 n M [ 3 H]raclopride (Perkin Elmer Life Sciences, Mass., USA) at room temperature.…”