Regional and subcellular compartmentation of the dopamine transporter and tyrosine hydroxylase in the rat ventral pallidum

The ventral pallidum (VP) is a major intermediary in the prefrontal cortical circuitry regulating sensorimotor gating and locomotor behavior, both of which are potently modulated by catecholamines. The VP catecholaminergic innervation is derived from midbrain dopaminergic neurons that differ in expression levels of the dopamine transporter (DAT) and from brainstem noradrenergic neurons without DAT. The preferentially low level of DAT in dopaminergic terminals in the prefrontal cortex and in striatal regions projecting more extensively to the VP medial (VPm) compared with VP lateral (VPI) compartment suggests possible region-specific differences in VP axonal distribution of DAT. To test this hypothesis, we examined the electron microscopic localization of DAT and the catecholamine-synthesizing enzyme, tyrosine hydroxylase (TH), in the VPm and VPl of rat brain. In both regions, DAT and TH were localized primarily in small unmyelinated axons and morphologically heterogeneous axon terminals. DAT-immunogold particles were few in number, but mostly located on the plasma membrane. In contrast, TH immunoreactivity was distributed in the cytoplasm of individual profiles, many of which were without detectable DAT. In comparison with TH, the mean area density of DAT-labeled axons was low throughout the VP. The mean area density of DAT-immunogold axon terminals, however, was significantly higher in VPI than in VPm, whereas that of TH-labeled axons was higher in VPm than in VPl. This dissociation suggests that, compared to the VPI, the VPm receives the greatest input from catecholaminergic afferents that are either nondopaminergic or characterized by having low levels or less terminal distributions of DAT. (C) 2003 Wiley-Liss, Inc.