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1. Using the rat exposed both acutely and chronically to lead as a model of lead neurotoxicity, various parameters of catecholamine metabolism were investigated. 2. The steady-state concentrations of noradrenaline, adrenaline and dopamine together with the activities of tyrosine hydroxylase and phenylethanolamine N-methyl transferase were measured in discrete brain nuclei--periventricular, paraventricular, median eminence, posterior and anterior hypothalamus, caudate putamen and globus pallidus. 3. Lead exposure resulted in significant fall in the activity of the rate-limiting enzyme of catecholamine synthesis, tyrosine hydroxylase which was associated with alterations in concentrations of catecholamines in the median eminence, periventricular nucleus and anterior hypothalamus. 4. No other brain nuclei investigated exhibited any effect of lead on the catecholaminergic nervous system and, therefore, the effect of lead on rat brain can be considered to be regionally specific.

Previous histological and histochemical studies have provided evidence that the globus pallidus (external pallidal segment) as conventionally delineated in the rat extends ventrally and rostrally beneath the transverse limb of the anterior commissure, invading the olfactory tubercle with its most ventral ramifications. This infracommissural subdivision of the globus pallidus or ventral pallidum (VP) is most selectively identified by being pervaded by a dense plexus of substance-P-positive striatofugal fibers; the extent of this plexus indicates that the VP behind the anterior commissure continues dorsally over some distance into the anteroventromedial part of the generally recognized (supracommissural) globus pallidus; the adjoining anterodorsolateral pallidal region, here named dorsal pallidum (DP), receives only few substance-P-positive fibers, but contains a dense plexus of enkephalin-positive striatal afferents that also pervades VP. Available autoradiographic data indicate that VP and DP receive their striatal innervation from two different subdivisions of the striatum: whereas VP is innervated by a large, anteroventromedial striatal region receiving substantial inputs from a variety of limbic and limbic-system-associated structures (and therefore called "limbic striatum"), DP receives its striatal input from an anterodorsolateral striatal sector receiving only sparse limbic afferents ("nonlimbic" striatum) but instead heavily innervated by the sensorimotor cortex. The present autoradiographic study has produced evidence that this dichotomy in the striatopallidal projection is to a large extent continued beyond the globus pallidus: whereas the efferents of DP were traced to the subthalamic nucleus and substantia nigra, those of VP were found to involve not only the subthalamic nucleus and substantia nigra but also the frontocingulate (and adjoining medial sensorimotor) cortex, the amygdala, lateral habenular and mediodorsal thalamic nucleus, hypothalamus, ventral tegmental area, and tegmental regions farther caudal and dorsal in the midbrain. These findings indicate that the ventral pallidum can convey striatopallidal outflow of limbic antecedents not only into extrapyramidal circuits but also back into the circuitry of the limbic system.

The origin of the cholinergic innervation to the amygdaloid complex was investigated with the use of acetylcholinesterase (AChE) histochemistry and choline acetyltransferase (ChAT) assay of microdissected nuclei. Visualization of AChE-positive neurones in the ventral forebrain was facilitated by pretreatment of rats with 1.5 mg/kg di-isopropyl phosphofluoridate (DFP). The AChE-positive neurones in the ventral forebrain are distributed in a continuous system from the septum through the lateral preoptic area to the entopeduncular nucleus caudally. Knife cuts or kainic acid injections (1.5 microgram/l microliter) placed in the lateral preoptic area resulted in substantial depletion of the AChE and ChAT content of the amygdala nuclei. Kainic acid injections (1.5 microgram/l microliter) in the diagonal band area or cuts through the stria terminalis dorsally did not significantly modify the AChE staining or ChAT content of the amygdala (although diagonal band injections partially depleted the hippocampus of ChAT). Knife cuts severing both the so-called ventral pathway and the stria terminalis did not produce significantly greater ChAT depletion in the amygdala than those produced by the knife cuts or kainic acid injections in the lateral preoptic area. Parasagittal knife cuts undercutting the lateral pyriform cortex also failed to modify the AChE or ChAT content of the amygdala, but they depleted the undercut cortex of both ChAT and AChE; AChE-positive material accumulated ventrally and medially to the knife cut. It is suggested that the major source of the cholinergic innervation of the amygdala is the magnocellular AChE-positive neurones in the lateral preoptic area and adjacent regions of the ventral forebrain.

The cat globus pallidus (GP) was found to contain both small and large cells that stain lightly and intensely for acetylcholinesterase (AChE), respectively. The small GP cells are similar to entopeduncular (EN) cells and it is proposed that both should be considered as 'typical' pallidal neurons. In contrast, large GP cells are similar to intensely stained AChE cells present in the substantia innominata (SI) and the putamen (PUT). Furthermore, HRP injection into the neocortex was found to label numerous large AChE cells in GP and a lesser number of similar neurons in PUT and SI. No HRP labeling was observed in the smaller cells of EN, GP and PUT. These findings suggest that the magnocellular AChE neurons in feline basal ganglia may be part of a single population of 'limbic' elements.

The pharmacohistochemical neuronal staining method for gamma-aminobutyric transaminase (GABA-T) combined with retrograde horseradish peroxidase (HRP) staining was used to define more precisely the descending striatonigral and pallidonigral pathways. Previous studies have established that GABA-T intensive cells in the basal ganglia and other structures correspond with reported glutamic acid decarboxylase (GAD)-containing cells and are therefore presumed to use GABA as their neurotransmitter. Following injection of HRP into the substantia nigra, many HRP-labeled cells were detected in the caudate-putamen and globus pallidus. Two separate groups of cells were doubly labeled for GABA-T and HRP and seemed to represent two distinct GABA-T-rich descending pathways to the substantia nigra. One component came from medium-sized cells in the lateral aspect of the globus pallidus. It represented a majority of all descending cells from that nucleus. The other came from the lateral aspect of the caudate-putamen and represented only a minority of descending cells from that structure. These data suggest that the majority of striatonigral fibers are non-GABA containing while the majority of pallidonigral fibers are GABA-containing. The precise location of the GABA-T intensive cells making up these two pathways helps to explain much confusing data in the literature on the source of descending GABA fibers to the substantia nigra.

The activity of angiotensin converting enzyme, which transforms the relatively inactive decapeptide angiotensin I to the active octapeptide angiotensin II by removal of an L-histidyl-L-leucine residue, has been assayed in numerous region of the calf brain and of the brains of humans with Huntington's chorea and controls. In calf brain there are pronounced regional variations in enzyme activity, with highest activity in the globus pallidus and area postrema. In human brain, enzyme activity is highest in the corpus striatum, with similar levels in the caudate, putamen, and globus pallidus. Converting enzyme activity is reduced by 83 to 92% in the globus pallidus in Huntington's chorea. The caudate and putamen of choreic patients display 62 to 69% reductions in enzyme activity. Converting enzyme activity in two cerebral cortical regions from choreic brains is not significantly different from control.

The diurnal rhythmicity of glutamic acid decarboxylase (GAD) activity in the nucleus level of the rat brain was examined by the radiochemical micromethod in a light-dark condition. GAD activity showed a biphasic variation in globus pallidus and substantia nigra (zona reticulata and compacta), but a monophasic variation, i.e. high in the dark, in colliculus superior (stratum griseum superficiale and stratum opticum). As for hypothalamus GAD activity of some nuclei (N. arcuatus, N. periventricularis, N. preopticus, etc.) it indicated a monophasic variation, while that of some nuclei (N. suprachiasmaticus, N. ventromedialis, A. lateralis, etc.) it showed no significant variations despite their proved functional activity with rhythmicity.

Post-mortem brain tissue from 7 patients who died with a diagnosis of senile dementia of Alzheimer type (SDAT) was compared with tissue obtained from 7 control patients at routine post mortem. A significant fall in choline acetyltransferase (ChAT) activity was apparent in the cerebral cortex of the SDAT cases which was maximal in the temporal lobe. The fall in ChAT activity was not accompanied by changes in cortical vasoactive intestinal polypeptide (VIP) measured by radioimmunoassay.