Clinical,biochemical, and hormonal aspects of treatment with des-tyr1-gamma-endorphin in schizophrenia

Des-tyr¹-y-endorphin (DTyE) was administered intramuscularly in a dose of 1 mg/day for 10 days to 18 neuroleptic-free schizophrenic patients in a double-blind crossover design. Six patients showed either a slight or no antipsychotic response; seven patients showed a moderate antipsychotic response; and the remaining five patients showed a marked antipsychotic response. DTyE led to a decrease of plasma prolactin levels in patients treated with DTyE in the first period of experimental treatment as compared to those treated with placebo. Neither plasma levels of growth hormone and cortisol nor cerebrospinal fluid concentrations of homovanillic acid, 5-hydroxyindoleactic acid, and 3-methoxy-4- hydroxyphenylglycol were affected by DTyE. Patients suffering from a hebephrenic or paranoid type of schizophrenia and those presenting relatively fewer negative symptoms were most susceptible to treatment with DTyE. These data confirm and extend previous findings that DTyE has antipsychotic properties in a number of schizophrenic patients.     

Effect of (Des-Tyr)-gamma-endorphin in schizophrenia

Des-tyrosine-gamma-endorphin (DT gamma E), a derivative of gamma-endorphin, which has been reported to have some neuroleptic-like properties in man, was administered to eight hospitalized schizophrenic patients (six chronic, one subacute, one acute) in an open study. Following an initial drug-free period, patients were given DT gamma E for 12 days in doses ranging from 1 to 10 mg/day. Two of the patients were markedly improved after receiving DT gamma E. The improvement was sustained for 2 months in one subjects, while the other deteriorated to pretreatment status within 48 hours of the discontinuation of DT gamma E. Of the other six patients, one showed moderate improvement, three showed minimal improvement, and two showed no change. Improvement was mainly in the area of social functioning; change in positive psychotic symptoms was less noticeable. The positive results obtained in this study in some subjects could have been nonspecific effects, rather than pharmacological action, since social functioning, the main area of improvement, may be especially sensitive to expectancy effects in open trials. Nevertheless, further study of DT gamma E in acute schizophrenics for longer periods appears indicated.     

Evidence for biochemical heterogeneity in schizophrenia: a multivariate study of monoaminergic indices in human post-mortal brain tissue

Summary A previously performedpost-mortem study comparing monoaminergic indices in the brains of 14 schizophrenic patients and 10 patients with psychosis not diagnosed as schizophrenia, with age-matched control cases without any known neuropsychiatric illness, was re-investigated, using multivariate analysis. The monoaminergic patterns showing up in this analysis suggested the existence of at least two different forms of the disease, both of which could be distinguished from the controls as well as from each other. One of the schizophrenic groups consisted of paranoid cases, and had a relatively mild family history, whereas the other group, mainly consisting of hebephrenic cases, had a severe family history. The former group showed low levels of dopamine and high levels of serotonergic precursor and metabolite, whereas the latter group in some respects tended to show the opposite aberrations. Neuroleptic treatment did not seem to account for the different biochemical profiles, unless one assumes that this treatment can cause completely different monoaminergic aberrations in different individuals. Instead, one could argue that the different biochemical profiles found are characteristic of the disease.The most salient parts of this material were presented at a symposium of depression held in Lund, Sweden on January 19, 1994     

Nα-Acetyl-Vasopressin- and Nα-Acetyl-Oxytocin-Like Substances: Isolation and Characterization in the Rat Neurointermediate Pituitary and Presence in the Brain

Post-translational modifications of vasopressin and oxytocin in pituitary and brain were investigated in view of recent evidence that oxytocin is partly N^α-acetyfated in the bovine pineal gland. Two peptides were isolated from the neurointermediate lobe of the rat pituitary gland and characterized as N^α-acetyl-vasopressin and N^α-acetyl-oxytocin, based on chromatographic and immunological properties as well as the blocked N-terminus. In the neurointermediate pituitary the acetylated forms represented approximately 1% of the vasopressin and oxytocin contents. These two peptides were also detected in some, but not all, investigated brain areas. The highest degree of acetylation was found in the pineal gland. In all regions acetylation of oxytocin was more abundant than that of vasopressin. The data indicate that acetylation of vasopressin and oxytocin generally occurs as a post-translational modification. They support the concept that acetylation may represent a mechanism aimed to control bioactivity of the neurohypophyseal hormones.     

Sex/gender differences in the brain and cognition in schizophrenia

The early conceptualizations of schizophrenia have noted some sex/gender differences in epidemiology and clinical expression of the disorder. Over the past few decades, the interest in differences between male and female patients has expanded to encompass brain morphology and neurocognitive function. Despite some variability and methodological shortcomings, a few patterns emerge from the available literature. Most studies of gross neuroanatomy show more enlarged ventricles and smaller frontal lobes in men than in women with schizophrenia; finding reflecting normal sexual dimorphism. In comparison, studies of brain asymmetry and specific corticolimbic structures, suggest a disturbance in normal sexual dimorphism. The neurocognitive findings are somewhat consistent with this picture. Studies of cognitive functions mediated by the lateral frontal network tend to show sex differences in patients which are in the same direction as those observed in the general population, whereas studies of processes mediated by the corticolimbic system more frequently reveal reversal of normal sexual dimorphisms. These trends are faint and future research would need to delineate neurocognitive differences between men and women with various subtypes of schizophrenia (e.g., early versus late onset), while taking into consideration hormonal status and gender of tested participants.     

Metabolic,hormonal and stress-related molecular changes in post-mortem pituitary glands from schizophrenia subjects

Abstract

Objectives. To identify a molecular profile for schizophrenia using post-mortem pituitaries from schizophrenia and control subjects. Methods. Molecular profiling analysis of pituitaries from schizophrenia (n = 14) and control (n = 15) subjects was carried out using a combination of liquid chromatography tandem mass spectrometry (LC-MS^E), multiplex analyte profiling (MAP), two-dimensional difference gel electrophoresis (2D-DIGE) and Western blot analysis. Results. This led to identification of differentially expressed molecules in schizophrenia patients including hypothalamic–pituitary–adrenal axis-associated constituents such as cortisol, pro-adrenocorticotropic hormone, arginine vasopressin precursor, agouti-related protein, growth hormone, prolactin and secretagogin, as well as molecules associated with lipid transport and metabolism such as apolipoproteins A1, A2, C3 and H. Altered levels of secretagogin in serum from a cohort of living first onset schizophrenia patients were also detected, suggesting disease association and illustrating the potential for translating some components of this molecular profile to serum-based assays. Conclusions. Future studies on the molecules identified here may lead to new insights into schizophrenia pathophysiology and pave the way for translation of novel diagnostics for use in a clinical setting.     

Lack of association of SLC1A1 variants with schizophrenia in Chinese Han population

In this study, we analyzed four single nucleotide polymorphisms (SNPs) (rs10491734, rs2228622, rs301430 and rs301443) of the solute carrier family 1 gene (SLC1A1) in a set of 616 schizophrenia patients and 638 matched healthy controls of Han Chinese descent. No significant differences of genotype or allele distribution were identified between the patients and controls. Our data suggest that SLC1A1 is unlikely to be a major susceptibility gene for schizophrenia in Han Chinese.     

Family-based association study of SELENBP1 in schizophrenia

The SELENBP1 gene previously was found to be up-regulated in microarray analysis of both peripheral blood cell and brain tissue samples from schizophrenia patients. Quantitative PCR analysis subsequently corroborated the altered expression of SELENBP1 in schizophrenia brain tissue samples from the Stanley Array Correction. The aim of this study was to extend those findings by employing family-based association methods to a sample of over 2400 individuals (including 1214 individuals affected by schizophrenia) of Han Chinese descent living in Taiwan. One of four haplotype-tagging SNPs and two different two-marker haplotypes showed nominally significant evidence for association with schizophrenia under an additive model, suggesting that genetic variation in SELENBP1 may influence risk for the disorder, while this significance did not remain when other inheritance models were considered. Further comprehensive analysis with other SNPs and haplotypes is needed and warranted.     

PACAP and VIP Stimulate Ca2+ Oscillations in Rat Gonadotrophs through the PACAP/VIP Type 1 Receptor (PVR1) Linked to a Pertussis Toxin-Insensitive G-Protein and the Activation of Phospholipase C-β

Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) are hypothalamic factors that play roles in the regulation of anterior pituitary cell activity. PACAP exists in 2 forms physiologically, a 38 amino acid form (PACAP38) and a form possessing the N-terminal 27 amino acids of PACAP38 (PACAP27). We have previously shown that PACAP38 stimulates an increase in [Ca²⁺]_i in rat gonadotrophs. In an attempt to identify the PACAP receptor type underlying this effect, we compared the potency of PACAP38, PACAP27 and VIP to stimulate Ca²⁺ changes in identified single rat gonadotrophs. All 3 peptides at 100  nM were capable of stimulating high amplitude Ca²⁺ oscillations, which were also observed in the absence of extracellular Ca²⁺. The order of potency of these peptides was PACAP38>PACAP27>VIP, and a potent antagonist of the PACAP/VIP type II binding site ([4-Cl-D-Phe⁶, Leu¹⁷]-VIP) failed to block these responses, suggesting that these effects are mediated through a PACAP/VIP type 1 receptor (PVR1). The Ca²⁺ responses to PACAP38 and VIP were unaffected by overnight treatment of the cells with pertussis toxin (PTX; 250  ng/ml) indicating that these responses are mediated by a PTX-insensitive G-protein. Finally, the Ca²⁺ responses stimulated by PACAP38 and VIP were blocked by the phospholipase C- β blocker U73122 (5  μM). In summary, PACAP stimulates Ca²⁺ oscillations in rat gonadotrophs through the activation of the PVR1 linked to a PTX-insensitive G-protein and the activation of phospholipase C- β . VIP can stimulate the same pathway in rat gonadotrophs, although it is at least 100 fold less potent than PACAP38.     

The Expression of Voltage-Gated Ca2+ Channels in Pituicytes and the Up-Regulation of L-Type Ca2+ Channels During Water Deprivation

The primary components of the neurohypophysis are the neuroendocrine terminals that release vasopressin and oxytocin, and pituicytes, which are astrocytes that normally surround and envelop these terminals. Pituicytes regulate neurohormone release by secreting the inhibitory modulator taurine in an osmotically‐regulated fashion and undergo a marked structural reorganisation in response to dehydration as well as during lactation and parturition. Because of these unique functions, and the possibility that Ca²⁺ influx could regulate their activity, we tested for the expression of voltage‐gated Ca²⁺ channel α1 subunits in pituicytes both in situ and in primary culture. Colocalisation studies in neurohypophysial slices show that pituicytes (identified by their expression of the glial marker S100β), are immunoreactive for antibodies directed against Ca²⁺ channel α1 subunits Ca_V2.2 and Ca_V2.3, which mediate N‐ and R‐type Ca²⁺ currents, respectively. Pituicytes in primary culture express immunoreactivity for Ca_V1.2, Ca_V2.1, Ca_V2.2, Ca_V2.3 and Ca_V3.1 (which mediate L‐, P/Q‐, N‐, R‐ and T‐type currents, respectively) and immunoblotting studies confirmed the expression of these Ca²⁺ channel α1 subunits. This increase in Ca²⁺ channel expression may occur only in pituicytes in culture, or may reflect an inherent capability of pituicytes to initiate the expression of multiple types of Ca²⁺ channels when stimulated to do so. We therefore performed immunohistochemistry studies on pituitaries obtained from rats that had been deprived of water for 24 h. Pituicytes in these preparations showed a significantly increased immunoreactivity to Ca_V1.2, suggesting that expression of these channels is up‐regulated during the adaptation to long‐lasting dehydration. Our results suggest that Ca²⁺ channels may play important roles in pituicyte function, including a contribution to the adaptation that occurs in pituicytes when the need for hormone release is elevated.     

Genetic polymorphisms in the dopamine-2 receptor (DRD2), dopamine-3 receptor (DRD3), and dopamine transporter (SLC6A3) genes in schizophrenia: Data from an association study

Objective

To investigate the association between dopaminergic polymorphisms [DRD2 −141C Ins/Del, DRD3 Ser9Gly, and SLC6A3 VNTR] and schizophrenia.

Methods

Two hundred and eighty-eight outpatients with schizophrenia (DSM-IV criteria) [mean age (SD) = 36.4 (12.4), 60.1% males] and 421 unrelated healthy controls [mean age (SD) = 40.6 (11.3), 51.3% males] from a homogeneous Spanish Caucasian population were genotyped using standard methods.

Results

There was a significant difference in genotype distribution for the DRD2 −141C Ins/Del polymorphism [(χ² (2) = 12.35, corrected p = 0.012]. The − 141C Del allele was more common in patients than in controls [0.19 vs. 0.13; χ² (1) = 9.14, corrected p = 0.018, OR (95% CI) = 1.57 (1.17–2.10)]. Genotype and allele distributions for DRD3 Ser9Gly and SLC6A3 VNTR polymorphisms were similar in both groups. However, there was tentative evidence of an interaction effect between DRD3 Ser9Gly and SLC6A3 VNTR [Wald = 9.56 (4), p = 0.049]. Compared to the SLC6A3 10/10 genotype category, the risk of schizophrenia was halved among those with 9/10 [OR = 0.51 (95% CI = 0.30–0.89), p = 0.017]. This protective effect was only present in combination with DRD3 Ser/Ser genotype because of the significant interaction between 9/10 and both Ser/Gly [OR = 2.45 (95% CI = 1.16–5.17), p = 0.019] and Gly/Gly [OR = 3.80 (95% CI = 1.24–11.63), p = 0.019].

Conclusions

This study provides evidence that a genetic variant in the DRD2 gene and possible interaction between DRD3 and SLC6A3 genes are associated with schizophrenia. These findings warrant examination in replication studies.     

Alpha-melanocyte-stimulating hormone (alpha-MSH) in the brain of the African lungfish, Protopterus annectens: immunohistochemical localization and biochemical characterization.

The distribution of alpha-melanocyte-stimulating hormone (alpha-MSH) containing neurons and the molecular forms of alpha-MSH-related peptides exhibit substantial differences in the brains of fish and amphibians. Lungfishes, which share similarities with both fishes and tetrapods, represent a valuable group in which to investigate the neuroanatomical and neurochemical facets of evolution. In the present study, we have localized and characterized alpha-MSH-immunoreactive peptides in the central nervous system of the African lungfish Protopterus annectens. Perikarya exhibiting alpha-MSH-like immunoreactivity were observed in two distinct regions of the hypothalamus: the rostral part of the preoptic nucleus and the caudal part of the hypothalamus. In the caudal hypothalamus most alpha-MSH-immunopositive perikarya were located in both the subependymal and deepest layers of the ventral periventricular region. Scattered alpha-MSH-immunopositive cells were occasionally detected in the dorsal side of the caudal hypothalamus. The alpha-MSH-immunoreactive material localized in the brain was characterized by combining high-performance liquid chromatography (HPLC) analysis and radioimmunological detection. The displacement curves obtained with synthetic alpha-MSH and serial dilutions of brain and pituitary extracts were parallel. HPLC analysis of lungfish hypothalamic extracts showed that the major immunoreactive peak coeluted with synthetic desacetyl alpha-MSH and its sulfoxide derivative. An additional peak coeluted with synthetic sulfoxide alpha-MSH. In contrast, in the pituitary, the predominant form of alpha-MSH-like material coeluted with the N,O-diacetyl alpha-MSH standard. These results provide the first evidence for the presence of alpha-MSH-related peptides in the brain of a lungfish. The distribution of alpha-MSH neuronal systems in the lungfish is very similar to that reported in amphibians, supporting the existence of phylogenetic convergences between these two vertebrate groups.     

Analyses of variants located in estrogen metabolism genes (ESR1, ESR2, COMT and APOE) and schizophrenia

Relationships between gender, age-of-onset of schizophrenia and reproductive age strongly suggest a key role for gonadal hormones, and more specifically for estrogens, in the etiology of the illness. Also, estrogens act as neural growth and trophic factors influencing neuron and glial cells in many areas of the central nervous system. Therefore, we investigated the association between schizophrenia and 4 genes related to estrogen metabolism. These genes are ESR1 (estrogen receptor 1), ESR2 (estrogen receptor 2), APOE (apolipoprotein E) and COMT (catechol-O-methyltransferase). The expression of APOE and COMT, which contain estrogen response elements, have been demonstrated to be regulated by the estrogen receptors. In this current association study, we examined 59 single nucleotide polymorphisms (SNPs) located in the ESR1 (26), ESR2 (14), APOE (7) and COMT (12) loci. Allele frequencies were evaluated in the schizophrenia (n = 585)-control (n = 615) sample and no association was found with any of the four genes. In conclusion, our data suggest that the four analyzed genes do not play an important role in susceptibility to schizophrenia.     

Effects of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) and Vasoactive Intestinal Polypeptide (VIP) on Prolactin, Luteinizing Hormone and Growth Hormone Secretion in the Ewe

This study was undertaken to investigate the roles of PACAP and VIP in the control of pituitary hormone secretion in the ewe. The first experiment was designed to identify any direct effects at the level of the pituitary and was conducted during the luteal phase of a prostaglandin-synchronized oestrous cycle. PACAP (0.008, 0.04, 0.2 and 1.0 nmol/min) or VIP (0.06, 0.2, 0.6 and 1.8 nmol/min) was infused into the carotid artery over a 10 min period. Blood samples were taken before and after the infusions so that plasma PRL, LH and GH concentrations could be measured. Blood pressure was also monitored to determine if the doses used were biologically active. In no case was an effect on hormone secretion observed. In contrast, the highest dose of each peptide induced an increase in heart rate to almost three-fold the resting value. Although both peptides are active in vivo, this result suggests that neither peptide has a direct effect on hormone release from the pituitary of prostaglandin-synchronized ewes. In a second experiment, we investigated whether the peptides had central effects on hormone secretion. Intracerebroventricular (ICV) injection of PACAP or VIP at the dose 10nmol was tested in ovariectomized ewes. After injection, PACAP suppressed PRL and GH secretion so that plasma hormone concentrations from 1–3 h after injection were significantly different from the control (P<0.05 for PRL, P<0.01 for GH). In addition, PACAP significantly reduced mean LH concentration (P<0.05) and LH pulse frequency (P<0.01). A similar suppressive effect on LH secretion was also observed after ICV injection of VIP (P<0.05 for both parameters), although PRL and GH release were not affected. These results suggest a possible role for PACAP in the neuroendocrine control of PRL, GH and LH secretion in sheep. In addition, VIP may be involved in the control of LH secretion. In contrast, there is no evidence to suggest that either peptide is a hypophysiotropic factor for PRL, LH or GH in prostaglandin-synchronized ewes.     

Perception of faces in schizophrenia: Subjective (self-report) vs. objective (psychophysics) assessments

ObjectivesFace perception impairment in schizophrenia has been demonstrated, mostly through experimental studies. How this laboratory-defined behavioral impairment is associated with patients’ perceptual experience of various faces in everyday life is however unclear. This question is important because a first-person account of face perception has direct consequences on social functioning of patients. In this study, we adapted and administered a self-reported questionnaire on narrative perceptual experience of faces along with psychophysical assessments of face perception in schizophrenia.MethodsThe self-reported questionnaire includes six rating items of face-related functioning in everyday life, providing a subjective measure of face perception. The psychophysical assessment determines perceptual threshold for discriminating different facial identities, providing an objective measure of face perception.ResultsCompared to controls (n = 25), patients (n = 35) showed significantly lower scores (worse performance) in the subjective assessment and significantly higher thresholds (worse performance) in the objective assessment. The subjective and objective face perception assessments were moderately correlated in controls but not in patients. The subjective face perception assessments were significantly correlated with measurements of a social cognitive ability (Theory of Mind), again in controls but not in patients.ConclusionThese results suggest that in schizophrenia the quality of face-related functioning in everyday life is degraded and the role that basic face discrimination capacity plays in face-related everyday functioning is disrupted.     

No difference in the prevalence of cavum septum pellucidum (CSP) between first-episode schizophrenia patients, offspring of schizophrenia patients and healthy controls

The reported prevalence of cavum septum pellucidum (CSP), is extremely variable (from 0.1% to 85%) depending upon the measurement method or imaging resolution. Higher prevalence of CSP has been found in schizophrenia. In this study, we examined the prevalence of CSP in a large number of first-episode schizophrenia patients, young relatives of schizophrenia patients and healthy controls. We manually measured CSP using 1.5 mm T1 MRI scans from ongoing studies at University of Pittsburgh in 89 first-episode patients with schizophrenia (age=23.8+/-7.4, M/F=61/28), 64 genetically at-risk individuals (offspring and siblings of schizophrenia patients, age 15.2+/-3.7, M/F=29/32) and 120 comparison subjects (n=120, age=22.1+/-7.9, M/F62/50). CSP was present in 64% of the first-episode patients (mean length 1.87+/-2.3 mm), 64.6% of the at-risk individuals (1.64+/-1.96 mm) and 64.2% of the normal controls (1.88+/-2.0 mm). There was no difference in the prevalence of CSP exceeding 4 mm. We also did not find any influence of the sex or age in the presence or size of CSP. Our data cast doubt on the significance of CSP as markers of neurodevelopmental pathology in schizophrenia.     

Effectiveness and tolerability of schizophrenia treatment in Central and Eastern Europe: results after 1 year from a prospective,observational study (IC-SOHO)

Objective. The Intercontinental Schizophrenia Outpatient Health Outcomes (IC-SOHO) study is intended to complement smaller, shorter-term observational studies and randomised controlled clinical trials in providing information on the treatment of schizophrenia in various geographies that have not been well studied previously.

Methods. Interim results after 12 months are presented for a subset of patients from eight Central and Eastern European (CEE) countries initiating or switching to olanzapine, risperidone, or typical antipsychotic monotherapy at Baseline (n=1387).

Results. Patients initially prescribed olanzapine and risperidone experienced significantly greater improvements in a broad range of schizophrenia symptom domains compared with patients prescribed typicals. Furthermore, patients in the olanzapine group showed significantly greater improvements in overall and negative symptom domains compared with the risperidone group (all P≤0.05). While patients in the olanzapine group gained more weight than the other two groups, they had significantly lower odds of developing extrapyramidal symptoms, loss of libido, and sexual dysfunction. Patients initially prescribed olanzapine were also significantly less likely to have changed or added antipsychotics during 12 months of treatment compared with the risperidone and typicals groups.

Conclusion. In this CEE sample, schizophrenia treatment outcomes after 12 months varied between patients initially prescribed different antipsychotics.     

Expression of Angiotensin Type-1 (AT1) and Type-2 (AT2) Receptor mRNAs in the Adult Rat Brain: A Functional Neuroanatomical Review

The discovery that all components of the renin–angiotensin system (RAS) are present in the central nervous system led investigators to postulate the existence of a local brain RAS. Supporting this, angiotensin immunoreactive neurons have been visualized in the brain. Two major pathways were described: a forebrain pathway which connects circumventricular organs to the median preoptic nucleus, paraventricular nucleus, and supraoptic nucleus, and a second pathway connecting the hypothalamus to the medulla oblongata. Blood–brain barrier deficient circumventricular organs are rich in angiotensin II receptors. By activating these receptors, circulating angiotensin II may act on central cardiovascular centers via angiotensinergic neurons, providing a link between peripheral and central angiotensin II systems. Among the effector peptides of the brain RAS, angiotensin II and angiotensin III have the same affinity for the two pharmacologically well-defined receptors: type 1 (AT1) and type 2 (AT2). When injected in the brain, these peptides increase blood pressure, water intake, and anterior and posterior pituitary hormone release and may modify memory and learning. The cloning of AT1 and AT2 receptor cDNAs has revealed that these receptors belong to the seven transmembrane domain receptor family. In rodents, two AT1 receptor subtypes, AT1A and AT1B, have been isolated. Using specific riboprobes forin situhybridization histochemistry, recent studies mapped the distribution of AT1A, AT1B, and AT2 receptor mRNAs in the adult rat and found a predominant expression of AT1A and AT2 mRNA in the brain and of AT1B in the pituitary. Very limited overlap was found between the brain expression of AT1A and AT2 mRNAs. In several functional entities of the brain, such as the preoptic region, the hypothalamus, the olivocerebellary system, and the brainstem baroreflex arc, the colocalization of receptor mRNA, binding sites, and angiotensin immunoreactive nerve terminals suggests local synthesis and expression of angiotensin II receptors. In other areas, such as the bed nucleus of the stria terminalis, the median eminence, or certain parts of the nucleus of the solitary tract, angiotensin II receptors are likely of extrinsic origin. The neuronal expression of AT1A and AT2 receptors was demonstrated in the subfornical organ, the hypothalamus, and the lateral septum. By using double labelin situhybridization, AT1A receptor expression was localized in corticotropin releasing hormone but not in vasopressin containing neurons in the hypothalamus. The information is discussed together with functional data concerning the role of brain angiotensins, in an attempt to provide a better understanding of the physiological and functional roles of each receptor subtype.