Light and electron microscopic localization of alpha-1 adrenergic receptor immunoreactivity in the rat striatum and ventral midbrain.

Electrophysiological and pharmacological studies have demonstrated that alpha-1 adrenergic receptor (alpha1AR) activation facilitates dopamine (DA) transmission in the striatum and ventral midbrain. However, because little is known about the localization of alpha1ARs in dopaminergic regions, the substrate(s) and mechanism(s) underlying this facilitation of DA signaling are poorly understood. To address this issue, we used light and electron microscopy immunoperoxidase labeling to examine the cellular and ultrastructural distribution of alpha1ARs in the caudate putamen, nucleus accumbens, ventral tegmental area, and substantia nigra in the rat. Analysis at the light microscopic level revealed alpha1AR immunoreactivity mainly in neuropil, with occasional staining in cell bodies. At the electron microscopic level, alpha1AR immunoreactivity was found primarily in presynaptic elements, with scarce postsynaptic labeling. Unmyelinated axons and about 30-50% terminals forming asymmetric synapses contained the majority of presynaptic labeling in the striatum and midbrain, while in the midbrain a subset of terminals forming symmetric synapses also displayed immunoreactivity. Postsynaptic labeling was scarce in both striatal and ventral midbrain regions. On the other hand, only 3-6% of spines displayed alpha1AR immunoreactivity in the caudate putamen and nucleus accumbens. These data suggest that the facilitation of dopaminergic transmission by alpha1ARs in the mesostriatal system is probably achieved primarily by pre-synaptic regulation of glutamate and GABA release.