Nucleus Interstitialis Striae Terminalis Research Articles

The involvement of dopaminergic systems with the stereotyped behaviour patterns induced by methylphenidate.

Abstract The electrolytic brain lesion technique was used to investigate the role of dopamine-containing areas and pathways in the rat for the mediation of methylphenidate stereotypy. Ablation of the dopaminergic pathways to the extrapyramidal areas at the level of the lateral hypothalamus or substantia nigra was without effect suggesting a postsynaptic site of action in the extrapyramidal nuclei. This site was shown to be the paleo- and not the neostriatum. Deafferentation of the mesolimbic nuclei abolished the weaker components of stereotypy in the acute phase. This effect was generally reflected by ablation of the tuberculum olfactorium but not by nucleus accumbens septi or nucleus interstitialis stria terminalis lesions. The action in the mesolimbic areas may, therefore, involve presynaptic mechanisms. Lesion of the nucleus amygdaloideus centralis abolished the intense components of stereotypy. The greater importance of extrapyramidal function for the action of methylphenidate would indicate a possible value for this agent in the treatment of Parkinson’s disease.

Quantitative immunohistochemical distribution of choline acetyltransferase in the rostral forebrain of the rat

The immunohistochemical distribution of choline acetyltransferase (CAT) in the rat rostral forebrain was analyzed quantitatively and minutely by means of a microphotometry system. The CAT concentrations varied greatly depending on the brain region. Within the neostriatum, CAT tended to be distributed with a lateral (high) to medial (low) gradient of approximately 1.2 : 1 and a caudal (high) to rostral (low) gradient of approximately 1.4 : 1, with the highest level in the medius lateralis. In the cortex cerebri, the CAT concentration in the area cinguli was high, while those in the area frontalis, area parietalis and area pyriformis were relatively low. High levels of CAT were also localized in other regions: e.g., hippocampus pars posterior, nucleus preopticus, nucleus anterior hypothalami, nucleus interstitialis striae terminalis, nucleus suprachiasmaticus and nucleus accumbens septi. The quantitative data obtained from the present microphotometric examination can be useful for analysis of a dynamic aspect of neurochemical substances under physiological as well as pathological conditions of the brain.

Sites of origin of gonadotropin releasing hormone containing projections to the amygdala and the interpenduncular nucleus

The sites of origin of gonadotropin releasing hormone (GnRH) containing projections to the amygdala and the interpenduccular nucleus were studied with immunofluorescence for GnRH in combination with retrograde transport of True blue. After small injections of True blue into the amygdala, retrogradely labeled GnRH producing neurons were identified in the rostral medial septum, the caudal roots of the nervus terminalus, diagonal band, nucleus triangularis septi, nucleus interstitialis striae terminalis, and in the ventrolateral hypothalamus. After injection of True blue into the interpendicular nucleus, a small GnRH producing cell group in the ventro-medial diagonal band, and certain GnRH-positive neurons in the ventral hypothalamus had retrogradely transported the dye. The results suggest a link between the amygdala and the nervus terminalis which is provided in part by GnRH-containing projections. The heterogeneity of the sites of origin of inputs to the amygdala and the interpenduncular nucleus indicates that the ‘behavioral’ component of the GnRH system is not restricted to a single brain nucleus, but it may be part of a diffuse network which has close anatomical ties with the ‘endocrine’ GnRH system.

Autoradiographic localization of D 1 dopamine receptors in the rat brain with [ 3H]SCH 23390

The regional distribution of D 1 dopamine (DA) receptors in the rat brain has been studied by quantitative autoradiography using the specific D 1 antagonist [ 3H]SCH 23390 as a ligand. The binding of [ 3H]SCH 23390 to striatal sections was saturable, stereospecific, reversible and of high affinity ( K d = 2.05nM); it occurred at single population of sites and possessed the pharmacological features of the D 1 DA receptor. The highest densities of [ 3H]SCH 23390 binding sites were found in the caudate-putamen, olfactory tubercle, nucleus accumbens and substantia nigra (especially in the pars compacta). High densities were also observed in the nucleus interstitialis striae terminalis, the anterior olfactory nucleus, the entopeduncular nucleus, the subthalamic nucleus, the claustrum and the amygdalohippocampal area. An intermediate labelling was found in the anteromedial and suprarhinal DA terminal fields of the cerebral cortex, the basolateral, medial and lateral amygdaloid nuclei, the endopiriform nucleus, the primary olfactory cortex, the globus pallidus, the superior colliculus (especially the superficial layer), the nucleus amygdaloideus corticalis and the dorsal hippocampus (molecular layer of the CA 1 and dentate gyrus). In the anteromedial and suprarhinal cortices, [ 3H]SCH 23390 binding was more concentrated in layers V and VI. Moderate levels of [ 3H]SCH 23390 were found in the thalamus, hypothalamus, the habenula, the ventral tegmental area, the posterior cingulate and entorhinal cortices, the supragenual dopamine terminal system and the cerebellum (molecular layer). This regional distribution of [ 3H]SCH 23390 closely correlated (except for the cerebellum) with the reported distribution of dopaminergic terminals. The topographical distribution of [ 3H]SCH 23390 has also been studied in detail in striatal subregions. The density of D 1 receptors was much greater in the ventrolateral sector and medial margin of the striatum than in the ventromedial and dorsolateral sectors. A rostrocaudal decrease in the densities of D 1 sites was also found along the rostrocaudal axis of the caudate-putamen. These lateral to medial and anteroposterior gradients overlapped with the density of the dopaminergic afferents.

Catechol estrogen formation by the CNS: regional distribution of estrogen-2/4-hydroxylase activity in rat brain.

Estrogen-2/4-hydroxylase (E-2/4-H) activity was measured by a direct product isolation assay in punch biopsy specimens obtained from nine nuclear regions from forebrain of adult male rats. Tritiated catechol estrogens were isolated from incubations of tissues with [6,7-3H]estradiol from all regions studied. The amount of 4-hydroxyestradiol (4-OH-E2) formed equaled or exceeded that of 2-hydroxyestradiol (2-OH-E2). There were significant regional differences in the amounts of catechol estrogen produced. The difference was nearly 8-fold between the arcuate-median eminence (ARC-ME) and the medial preoptic nucleus (POM), regions with the highest and lowest specific activities, respectively (37.7 +/- 6.2 vs. 5.1 +/- 0.7 pmol/mg protein/10 min 2-OH-E2, mean + SEM, n = 6). The supraoptic nucleus was the site of second highest concentrations of E-2/4-H activity (20.3 pmol 2-OH-E2/mg protein/10 min). Estrogen-2/4-H activity in the paraventricular (PVN) and periventricular (PERI) nuclear regions, though only about half that in the SON, was significantly greater than in the remaining brain areas (nucleus interstitialis striae terminalis, caudate, anterior hypothalamic and medial preoptic nuclei and cortex. The ARC-ME, the region with the highest E-2/4-H activity is where the dopaminergic neurones and terminals from the Gn-RH neurons are concentrated. The functions regulated by these two classes of neurones, the secretion of prolactin and gonadotrophins, respectively, have been the subject of most of the previous studies aimed at establishing the role of catechol estrogen formation in the hypothalamus.(ABSTRACT TRUNCATED AT 250 WORDS)

Distribution of atrial natriuretic factor-like immunoreactive neurons in the rat brain

Using antisera generated in rabbits against rat atriopeptin III [α-rANP(5–28)] and human α-atrial natriuretic polypeptide we mapped the distribution of atrial natriuretic factor-like immunoreactivity throughout the rat central nervous system. Cell bodies were observed in the telencephalon (nucleus interstitialis striae terminalis and between the amygdala centralis and medialis), throughout the diencephalon in all nuclei of the “anteroventral third ventricle”, the base of the hypothalamus, the subzona incerta area, the medial forebrain bundle and the medial habenula, in the mesencephalon (mamillary body, substantia nigra lateralis, dorsal and ventral parabrachial nuclei) and very sparse in the medulla oblongata along the fourth ventricle towards the vestibular nuclei, the nucleus tractus solitarii and nervi trigemini. Fibers were present wherever cell bodies were located. The highest relative densities were observed in the anteroventral third ventricle area and the medial habenula. Sparse fibers were also seen in the spinal cord (dorsal and ventral horn and around the central canal) and in the posterior pituitary. The predominance of the atrial natriuretic factor-like perikarya and fibers in the anteroventral third ventricle area suggests an involvement of this peptide in central blood pressure control.

Pharmacological profile of wet-dog shaking induced by electrical stimulation of the fornix in rats

Electrical stimulation of the fornix evoked body shaking in conscious rats. Stimulation of nucleus interstitialis stria terminalis failed to cause shaking. Fornix-evoked shaking was most consistently inhibited by drugs that modify brain noradrenergic function.

Distribution of enkephalin-related peptides in rat brain: Immunohistochemical studies using antisera to Met-enkephalin and Met-enkephalin Arg 6Phe 7

The enkephalin-related heptapeptide, Tyr-Gly-Gly-Phe-Met-Arg-Phe, forms the C-terminus of a biosynthetic precursor that contains both Met-enkephalin and Leu-enkephalin sequences. We have studied the distribution of heptapeptide-like immunoreactivity in rat brain by immunohistochemistry using a C-terminal specific antiserum. The results were compared with those obtained using an antiserum specific for the C-terminus of Met-enkephalin which does not react with C-terminally-extended variants. Both antisera specifically stained cell bodies and fibres in many regions of the rat central nervous system. Colchicine was needed for the demonstration of cell bodies with the Met-enkephalin antiserum, but not for the heptapeptide antiserum. In the nucleus of the solitary tract, in the commissural nucleus, the nucleus raphe obscurus and in the hypothalamus, studies of serial sections and re-staining experiments indicated that the two antisera stained the same cell bodies. However, in the olfactory bulb, the anterior olfactory nucleus, the olfactory tubercle, the nucleus accumbens, caudate-putamen, central nucleus of the amygdala, nucleus interstitialis striae terminalis, pre-lateral mamillary nuclei, ventral hypothalamus, hippocampus, peri-aqueductal grey and the granular layer of the cerebellum, cells were stained by the heptapeptide antiserum but not the Met-enkephalin antiserum. The two antisera revealed similar patterns of staining of nerve fibres in many regions including hypothalamus, central nucleus of the amygdala, lateral septum, thalamus, mid-brain and spinal cord. But in other areas notably, pallidum, caudate-putamen, substantia inominata, nucleus of the solitary tract and commissural nucleus, there were abundant fibres and terminals revealed by the Met-enkephalin antiserum but not by the heptapeptide antiserum. The results are discussed with respect to possible patterns of enkephalin biosynthesis; it is suggested that in some neurones immunoreactive enkephalin precursors terminating in the heptapeptide sequence are processed to produce the heptapeptide which is stored in terminals and is available for release as an endogenous opioid agonist in its own right. In other cases, however, it is suggested that the heptapeptide might be cleaved by removal of -Arg-Phe to yield Met-enkephalin which is the primary opioid product of this class of neurone.

Distribution of immunoreactive dynorphin in discrete brain nuclei; comparison with vasopressin

The distribution of the opioid peptide, dynorphin, has been studied in discrete, microdissected hypothalamic nuclei, and compared with the distribution of vasopressin. Both peptides were found in relatively high concentration in the supraoptic and paraventricular nuclei. However, dynorphin-like immunoreactivity (DYN-LI) was much more widely distributed in the hypothalamus than vasopressin-like immunoreactivity, with highest concentrations in the anterior hypothalamic and ventromedial nuclei. DYN-LI was also observed in some extra-hypothalamic structures; concentrations which were comparable to the highest levels in the hypothalamus were found in the tractus diagonalis and the nucleus interstitialis stria terminalis. Among the three brainstem nuclei examined, DYN-LI levels were highest in the sensory nucleus of the trigeminal nerve.

Changes in dopamine, noradrenaline and adrenaline in specific septal and preoptic nuclei after acute immobilization stress.

Acute immobilization stress results in changes in the concentration of both dopamine and noradrenaline in specific forebrain limbic system areas, whereas the adrenaline levels remain unchanged. Changes in dopamine concentrations are more restricted than those in noradrenaline concentrations. Dopamine levels are increased in the nucleus preopticus medialis, 2 and 4 h after stress, and decreased in the nucleus septalis lateralis, throughout the acute stress period. The noradrenaline levels are also increased in the nucleus preopticus medialis 2 and 4 h after stress. In most septal stress, and in the nucleus interstitialis striae terminalis, the noradrenaline levels are decreased early during acute stress, but return to normal values after 2-4 h of continuous stress. In the nucleus septalis intermediate, on the other hand, the noradrenaline levels are increased, and the change occurs only after 4 h of stress. These results suggest a participation of both noradrenaline levels are increased, and the change occurs only after 4 h of stress. These results suggest a participation of both noradrenaline levels are increased, and the change occurs only after 4 h of stress. These results suggest a participation of both noradrenaline and dopamine neurons in the central response to the stress reaction and the existence of fast adaptive changes in the metabolism of these biogenic amines in specific areas of the limbic system during stress.

Effect of des-tyr 1-γ-endorphin and des-tyr 1-α-endorphin on α-MPT-induced catecholamine disappearance in rat brain nuclei: A dose-response study

The effect of des-Tyr 1-γ-endorphin (ß-LPH 62–77, DTγE) and des-Tyr 1-α-endorphin (ß-LPH 62–76, DTαE), administered intracerebroventricularly (icv) in doses of 0.01, 0.1, 1 and 10 μg, was studied on the α-methyl-p-tyrosine- (α-MPT) induced disappearance of catecholamines in a number of microdissected rat brain regions, which were selected on the basis of the neuroanatomy of the dopamine systems in the brain and of previous observations. A dose-dependent increase in the disappearance of dopamine in α-MPT-pretreated rats was observed following icv administration of DTγE in the nucleus interstitialis striae terminalis, the paraventricular nucleus, the anterior hypothalamic nucleus and the zona incerta. In these same brain regions a decrease in the α-MPT-induced disappearance of dopamine was found following the administration of DTαE, but only after doses of 0.01, 0.1 and 1 μg. In none of these regions were effects observed after 10 μg of DTαE. No effects were seen on dopamine utilization in the nucleus accumbens, caudate nucleus and median eminence after any of the doses of DTγE or DTαE. The α-MPT-induced disappearance of noradrenaline was significantly enhanced in the anterior hypothalamic nucleus of rats treated with DTγE. It is concluded that DTγE and DTγE induce opposite changes in the utilization of dopamine selectively in brain regions which are predominantly innervated byneurons belonging to the intradiencephalic dopamine systems.

Mapping of motilin-immunoreactive Neurons of the rat brain

Motilin immunofluorescence was observed in the rat brain by means of N- and C-terminally directed antisera. A detailed mapping of the localization of motilin-like immunoreactive neurons in the rat forebrain is presented. Colchicine pretreatment revealed many cell bodies in the mediobasal hypothalamus. A small number of cells were observed in the organum vasculosum lamina terminalis (OVLT) region. A rich innervation of varicose fibers was observed in the median eminence and OVLT. Fibers of varying densities were observed in the preoptic area, nucleus interstitialis stria terminalis, hypothalamic nuclei, basal hypothalamus, amygdala, mammillary doby and central gray. The localization of these neurons suggests that motilin, like other brain peptides serves a variety of functions including neuroendocrine regulation.

The distribution of bovine pancreatic polypeptide-like immunoreactive neurons in rat brain

Using the indirect immunofluorescent technique, bovine pancreatic polypeptide (BPP)-like immunoreactive nerve fibers and cell bodies were observed widely distributed in rat brain. A detailed stereotaxic atlas of BPP-immunoreactive neurons was prepared. Large numbers of BPP-containing perikarya were observed in the acute nucleus, with scattered cells in the cerebral cortex, nucleus olfactorius anterior, nucleus tractus diagonalis, olfactory tubercle, nucleus accumbens, neostriatum, nucleus interstitialis stria terminalis, nucleus preopticus medialis, area retrochiasmatica, zona interna of the median eminence, substantia grisea centralis, locus coeruleus, nucleus tractus solitarius, and in the region of the nucleus reticularis lateralis. Large numbers of varicose BPP-like nerve fibers were observed in the following nuclei: accumbens, interstitialis stria terminalis, preopticus medialis, preopticus suprachiasmaticus, suprachiasmaticus, periventricular thalamic and hypothalamic, paraventricularis, dorsomedialis, ventromedialis, arcuatus, parabrachialis dorsalis, tractus solitarius and the substantia gelatinosa trigemini. The present findings suggest that a BPP-like peptide may be involved in significant neuronal circuitry, possibly in a neurotransmitter or neuromodulator role. However, the exact identity of this peptide and its physiological role remain to be determined.

Effects of chronic estrogen treatment on dopamine concentrations and turnover in discrete brain nuclei of ovariectomized rats

We investigated the effects of chronic estrogen treatment in ovariectomized rats on the concentration of dopamine in 33 discrete brain nuclei. In order to assess estrogen's influence on dopamine turnover, some of the rats were administered α-methyl-p-tyrosine. Estrogen treatment reduced the concentrations of dopamine in the nucleus accumbens septi, striatum, median eminence, nucleus anterior hypothalami, nucleus suprachiasmaticus, nucleus arcuate IV-V, area ventralis tegmenti, interpeduncular nucleus and nucleus interstitialis striae terminalis. Treatment was without effect on dopamine turnover in all areas studied.

Effects of α-endorphin, β-endorphin and (des-tyr 1)-γ-endorphin on α-MPT-induced catecholamine disappearance in discrete regions of the rat brain

Following the intracerebroventricular administration of α-endorphin, β-endorphin and (des-tyrosine 1 )-γ-endorphin in a dose of 100 ng, the α-MPT-induced catecholamine disappearance was found to be altered in discrete regions of the rat brain. In the regions in which α-endorphin exerted an effect, it without exception caused a decrease in catecholamine disappearance. Thus, in rats treated with α-endorphin the disappearance of noradrenaline was decreased in the medial septal nucleus, dorsomedial nucleus, central amygdaloid nucleus, subiculum, the ventral part of the nucleus reticularis medullae oblongatae and the A1 region, and that of dopamine in the caudate nucleus, globus pallidus, medial septal nucleus, nucleus interstitialis striae terminalis, paraventricular nucleus, zona incerta and central amygdaloids nucleus. β-endorphin was found to decrease noradrenaline disappearance in the ventral part of the nucleus reticularis medullae oblongatae, dopamine disappearance in the lateral septal nucleus and the disappearance of both amines in the rostral part of the nucleus tractus solitarii. Dopamine disappearance was increased in the medial septal nucleus and the zona incerta following β-endorphin treatment. Following treatment with (des-tyrosine 1 )-γ-endorphin, noradrenaline disappearance was enhanced in the anterior hypothalamic nucleus, whereas dopamine disappearance was increased in the paraventricular nucleus, the zona incerta and the rostral part of the nucleus tractus solitarii. In addition to this the latter peptide also caused a decreased noradrenaline disappearance in the periventricular thalamus and the A7 region. The results fit well with the suggestion that endorphins act as modulators of catecholamine neurotransmission in particular brain regions. The pattern of effects of the endorphins differ from that previously observed following intracerebroventricular administration of methionine-enkephalin. This is in keeping with the notion that the enkephalin containing network in the brain and that containing β-LPH represent two independent systems with distinct differences in their projections to various brain regions.

Identification, characterization and stereotaxic mapping of intraneuronal α-melanocyte stimulating hormone-like immunoreactive peptides in discrete regions of the rat brain

A highly specific antibody to α-melanocyte stimulating hormone (α-MSH) was used to histochemically localize and biochemically identify and quantitate α-MSH immunoreactivity in nerve fibers and cell bodies of the rat brain. α-MSH-like immunoreactivity was contained in fibers throughout the brain. The distribution of α-MSH was determined by immunocytochemistry as well as by radioimmunoassay combined with microdissection techniques. High concentrations of α-MSH were contained in the nucleus interstitialis stria terminalis, the median eminence and the medial preoptic, anterior hypothalamic, periventricular, paraventricular, arcuate, dorsomedial, and posterior hypothalamic nuclei. Moderate α-MSH concentrations were noted in the amygdala, septum, central gray, dorsal raphe, and the nucleus tractus solitarius. Cell bodies containing α-MSH were observed only in the arcuate nucleus. The α-MSH-like compound in brain had similar immunochemical and electrophoretic properties of standard α-MSH but high pressure liquid chromatographic analysis demonstrated that the α-MSH-like immunoreactivity was comprised of one major and two minor components. The major immunoreactive peak had an identical retention time as α-MSH and therefore may be chemically identical to α-MSH. The similar retention times and immunoreactivity of the other two compounds suggest a similarity in size and structure to α-MSH. These observations demonstrate that fibers containing α-MSH emanate from the arcuate nucleus to innervate many other regions of the rat brain.

Biochemical mapping of the noradrenergic ventral bundle projection sites: Evidence for a noradrenergic-dopaminergic interaction

Norepinephrine (NE) and dopamine (DA) concentration and dopamine turnover were measured 12 days after a unilateral or bilateral noradrenergic ventral bundle (VB) transection to determine the noradrenergic projection sites and possible interactions with dopaminergic systems. Both bilateral and unilateral VB transection resulted in a significant reduction of NE of the nucleus accumbens, lateral septal nucleus, medial forebrain bundle, ventromedial nucleus, dorsomedial nucleus and medial amygdaloid nucleus. Bilateral transection also decreased NE content of the median eminence and the periventricular and arcuate nuclei. In the medial preoptic nucleus, the nucleus interstitialis striae terminalis and the central gray catecholamine area, bilateral transection significantly decreased NE concentrations while unilateral lesions had no significant effect. The anterior hypothalamic, lateral preoptic, and paraventricular nuclei responded to bilateral VB transection with a decrease in NE concentration and to unilateral lesion with a bilateral increase in NE. In the dorsal hippocampus and the caudate nucleus, bilateral lesions had no effect on NE concentrations while unilateral transection significantly decreased NE concentrations. Regions in which neither bilateral nor unilateral VB transection produced a significant change in NE content are the olfactory tubercle, the nucleus tractus diagonalis, substantia nigra pars compacta and reticulata, ventral tegmental area, habenula, superior colliculus, and the cingulate and piriform cortices. Transection of the noradrenergic ventral bundle also produced changes in dopaminergic systems suggesting a noradrenergic-dopaminergic interaction. Bilateral VB transection decreased the dopamine concentration and turnover in the nucleus accumbens, increased steady-state levels and turnover in the nucleus tractus diagonalis and increased dopamine concentration in the lateral septum. Unilateral VB transection decreased DA concentration bilaterally in the caudate nucleus, olfactory tubercle, nucleus accumbens and the nucleus interstitialis striae terminalis but increased concentrations in the substantia nigra pars reticulata (ipsilateral) and in the ventral tegmental area (bilateral). These results indicate a broad projection field for the noradrenergic ventral bundle and suggest a noradrenergic-dopaminergic interaction.

Alpha-Melanocyte stimulating hormone: immunohistochemical identification and mapping in neurons of rat brain.

alpha-Melanocyte stimulating hormone (alpha-melanotropin) immunofluorescence was observed in rat brain by means of a highly specific and well-characterized antibody. The hormone was contained in arcuate nucleus cell bodies and in varicose fibers. Dense populations of hormone-containing fibers were present in the septum, the nucleus interstitialis stria terminalis, and the medial preoptic, anterior hypothalamic, dorsomedial, and periventricular nuclei. Moderate numbers of fibers were seen in the paraventricular and arcuate nuclei, the amygdala, the region of the tractus diagonalis, the mammillary body, the central gray, the cuneiform nucleus, and the nucleus of the solitary tract. There is an interesting correlation of alpha-melanocyte stimulating hormone fibers with regions of noradrenergic axonal projections and terminal fields.

Distribution of substance P-like immunoreactivity in the central nervous system of the rat—II. Light microscopic localization in relation to catecholamine-containing neurons

A comparison of the distribution of material reacting with antisera to substance P and tyrosine hydroxylase, respectively, was made on adjacent sections of the central nervous system of untreated rats using Coon's indirect immunofluorescence technique. In some cases correlations between the two antisera were made on the same section. Tyrosine hydroxylase was used as a marker for catecholamine-containing neurons. All catecholamine-containing cell groups (A1–A15) were surrounded by substance P-positive nerve terminals. A very high or high density of substance P-containing fibers was observed around the A9 dopaminergic cells and their dendrites in the substantia nigra and around the A2 catecholamine-containing cells in the nucleus commissuralis, the nucleus tractus solitarii and the nucleus originis dorsalis nervi vagi. Only occasional substance P-immunoreactive fibers were observed around tyrosine hydroxylase-positive cells in the area postrema and around the periglomerular dopamine cells in the olfactory bulb. The remaining catecholamine-containing groups of cells were surrounded by substance P-networks of a low or medium density. The relation of catecholamine-con-taining nerve terminals to substance P-immunoreactive cell bodies has not been analysed. There are certain areas where both substance P and tyrosine hydroxylase immunoreactive terminal networks were seen including the medial frontal cortex, the amygdaloid complex, particularly the central nucleus, the caudate nucleus, the nucleus accumbens, the lateral septal nucleus, the nucleus interstitialis striae terminalis, various hypothalamic nuclei, the periaqueductal central gray, the parabrachial nucleus, the nucleus tractus solitarii, the nucleus originis dorsalis nervi vagi and the spinal cord. Although overlap between the two systems occurred, a close analysis sometimes revealed differential distribution patterns. The results suggest that interaction of at least two types may occur between the two systems. Firstly, substance P-containing nerve terminals may innervate catecholamine-containing cells and, secondly, substance P-containing and catecholamine-containing nerve terminals may together influence neuronal activity in certain brain regions. The morphological relations between these two systems can, however, only be fully understood after ultrastructural investigations.

Central control of hepatic steroid metabolism: effect of discrete hypothalamic lesions.

The effects of various hypothalamic lesions on hepatic steroid metabolism in adult rats were investigated. It was found that frontal deafferentation at the retrochiasmatic and suprachiasmatic level resulted in a complete "feminization" of hepatic steroid metabolism in male rats. Such an effect was also seen when lesions involving mainly the anterior periventricular hypothalamic area and the suprachiasmatic nucleus were performed in male rats. Midline lesions, anterior to the suprachiasmatic nucleus, on the other hand, did not result in any significant effects. A moderate degree of "feminization" was obtained after bilateral lesions involving mainly the nucleus interstitialis striae terminalis but including also parts of the anterior commissure. Small lesions in the lateral preoptic area were, however, without effect. No effects were seen of analogous lesions in female rats in any of the cases studied. The present findings suggest that a region including the anterior hypothalamic periventricular area, the suprachiasmatic nucleus and adjacent areas is involved in the control of hepatic steroid metabolism. It is postulated that the neuronal cell bodies that produce a factor with an inhibitory effect on the secretion of "feminizing factor" have their origins in this area of the hypothalamus, or, alternatively, may send axons through this area to the basal hypothalamus and thus directly or indirectly influence the anterior pituitary gland.