Neurons exhibiting dopamine d 2 receptor immunoreactivity in the substantia nigra of the mutant weaver mouse

Abstract

Neurons exhibiting D 2 receptor-like immunoreactivity were investigated in the substantia nigra pars compacta of weaver mice at the light and electron microscope levels using immunocytochemical techniques. At the light microscope level, there was significant loss of D 2-like immunoreactive cells in weaver mice and the remaining labeled cells exhibited less intense immunoreactivity. At the ultrastructural level, there was a decrease in the number of immunoreactive profiles and fewer synapses were observed abutting labeled dendritic profiles. In addition, degenerative changes were noted in some of the D 2 receptor-like immunoreactive profiles. Double labeling with D 2 and tyrosine hydroxylase indicated that the majority of the labeled profiles were double labeled. Eight-week-old homozygous weavers were paired with wild-type littermates as controls and perfused with a buffered solution of acrolein/paraformadehyde. Midbrain sections were reacted immunocytochemically either with an antiserum to D 2 or with antisera to D 2 and tyrosine hydroxylase, using a double-labeling technique. Sections were processed for light and electron microscopy by standard methods. The results of this study confirm the autoreceptor-like activity of D 2 receptors on nigral dopamine neurons. The cell degeneration, down-regulation of D2 receptors, and decreased dendritic and synaptic components in the neuropil suggest that the synaptic integrity of the substantia nigra has been compromised, which in turn would affect the functional efficacy of the basal ganglia circuitry. This altered circuity is expressed in the Parkinson-like symptoms displayed by this mutant mouse.