Fourth Ventricle Of Brain Research Articles

Microdissection and Whole Mount Scanning Electron Microscopy Visualization of Mouse Choroid Plexus.

The choroid plexus (CP), a highly vascularized structure protruding into the ventricles of the brain, is one of the most understudied tissues in neuroscience. As it is becoming increasingly clear that this tiny structure plays a crucial role in health and disease of the central nervous system (CNS), it is of utmost importance to properly dissect the CP out of the brain ventricles in a way that allows downstream processing, ranging from functional to structural analysis. Here, isolation of the lateral and fourth brain ventricle mouse CP without the need for specialized tools or equipment is described. This isolation technique preserves the viability, function, and structure of cells within the CP. On account of its high vascularization, the CP can be visualized floating inside the ventricular cavities of the brain using a binocular microscope. However, transcardial perfusion required for downstream analysis can complicate the identification of the CP tissue. Depending on the further processing steps (e.g., RNA and protein analysis), this can be solved by visualizing the CP via transcardial perfusion with bromophenol blue. After isolation, the CP can be processed using several techniques, including RNA, protein, or single cell analysis, to gain further understanding on the function of this special brain structure. Here, scanning electron microscopy (SEM) on whole mount CP is used to get an overall view of the structure.

The Up-regulation of TNF-α Maintains Trigeminal Neuralgia by Modulating MAPKs Phosphorylation and BKCa Channels in Trigeminal Nucleus Caudalis.

Trigeminal neuralgia (TN) is a severe chronic neuropathic pain. Despite numerous available medical interventions, the therapeutic effects are not ideal. To control the pain attacks, the need for more contemporary drugs continues to be a real challenge. Our previous study reported that Ca2+-activated K+ channels (BKCa) channels modulated by mitogen-activated protein kinases (MAPKs) in the trigeminal ganglia (TG) neurons play crucial roles in regulating TN, and some research studies demonstrated that inflammatory cytokine tumor necrosis factor alpha (TNF-α) could promote neuropathic pain. Meanwhile, the trigeminal nucleus caudalis (TNC), the first central site of the trigeminal nociceptive pathway, is responsible for processing sensory and pain signals from the peripheral orofacial area. Thus, this study is aimed to further investigate whether TNF-α and MAPKs phosphorylation in the TNC could mediate the pathogenesis of TN by modulating BKCa channels. The results showed that TNF-α of the TNC region is upregulated significantly in the chronic constriction injury of infraorbital nerve (ION-CCI) rats model, which displayed persistent facial mechanical allodynia. The normal rats with target injection of exogenous TNF-α to the fourth brain ventricle behaved just like the ION-CCI model rats, the orofacial mechanical pain threshold decreased clearly. Meanwhile, the exogenous TNF-α increased the action potential frequency and reduced the BKCa currents of TNC neurons significantly, which could be reversed by U0126 and SB203580, the inhibitors of MAPK. In addition, U0126, SB203580, and another MAPK inhibitor SP600125 could relieve the facial mechanical allodynia by being injected into the fourth brain ventricle of ION-CCI model rats, respectively. Taken together, our work suggests that the upregulation of TNF-α in the TNC region would cause the increase of MAPKs phosphorylation and then the negative regulation of BKCa channels, resulting in the TN.

Shear-Induced Amyloid Aggregation in the Brain: V. Are Alzheimer's and Other Amyloid Diseases Initiated in the Lower Brain and Brainstem by Cerebrospinal Fluid Flow Stresses?

Amyloid-β (Aβ) and tau oligomers have been identified as neurotoxic agents responsible for causing Alzheimer’s disease (AD). Clinical trials using Aβ and tau as targets have failed, giving rise to calls for new research approaches to combat AD. This paper provides such an approach. Most basic AD research has involved quiescent Aβ and tau solutions. However, studies involving laminar and extensional flow of proteins have demonstrated that mechanical agitation of proteins induces or accelerates protein aggregation. Recent MRI brain studies have revealed high energy, chaotic motion of cerebrospinal fluid (CSF) in lower brain and brainstem regions. These and studies showing CSF flow within the brain have shown that there are two energetic hot spots. These are within the third and fourth brain ventricles and in the neighborhood of the circle of Willis blood vessel region. These two regions are also the same locations as those of the earliest Aβ and tau AD pathology. In this paper, it is proposed that cardiac systolic pulse waves that emanate from the major brain arteries in the lower brain and brainstem regions and whose pulse waves drive CSF flows within the brain are responsible for initiating AD and possibly other amyloid diseases. It is further proposed that the triggering of these diseases comes about because of the strengthening of systolic pulses due to major artery hardening that generates intense CSF extensional flow stress. Such stress provides the activation energy needed to induce conformational changes of both Aβ and tau within the lower brain and brainstem region, producing unique neurotoxic oligomer molecule conformations that induce AD.

Surgical treatment and prognosis of adult patients with brainstem gliomas

The paper presents 47 adult patients who were surgically treated due to brainstem gliomas. Thirteen patients presented with contrast-enhancing Grades III and IV gliomas, according to the WHO classification, 13 patients with contrast-enhancing tumours originating from the glial cells (Grade I; WHO classification), 9 patients with diffuse gliomas, 5 patients with tectal brainstem gliomas and 7 patients with exophytic brainstem gliomas. During the surgical procedure, neuronavigation and the diffusion tensor tractography (DTI) of the corticospinal tract were used with the examination of motor evoked potentials (MEPs) and somatosensory evoked potentials (SSEPs) with direct stimulation of the fundus of the fourth brain ventricle in order to define the localization of the nuclei of nerves VII, IX, X and XII. Cerebellar dysfunction, damage to cranial nerves and dysphagia were the most frequent postoperative sequelae which were also the most difficult to resolve. The Karnofsky score established preoperatively and the extent of tumour resection were the factors affecting the prognosis. The mean time of progression-free survival (14 months) and the mean survival time after surgery (20 months) were the shortest for malignant brainstem gliomas. In the group with tectal brainstem gliomas, no cases of progression were found and none of the patients died during the follow-up. Some patients were professionally active. Partial resection of diffuse brainstem gliomas did not prolong the mean survival above 5 years. However, some patients survived over 5 years in good condition.

The Reissner Fiber in the Cerebrospinal Fluid Controls Morphogenesis of the Body Axis

SummaryOrgan development depends on the integration of coordinated long-range communication between cells. The cerebrospinal fluid composition and flow properties regulate several aspects of central nervous system development, including progenitor proliferation, neurogenesis, and migration [1, 2, 3]. One understudied component of the cerebrospinal fluid, described over a century ago in vertebrates, is the Reissner fiber. This extracellular thread forming early in development results from the assembly of the SCO-spondin protein in the third and fourth brain ventricles and central canal of the spinal cord [4]. Up to now, the function of the Reissner fiber has remained elusive, partly due to the lack of genetic invalidation models [4]. Here, by mutating the scospondin gene, we demonstrate that the Reissner fiber is critical for the morphogenesis of a straight posterior body axis. In zebrafish mutants where the Reissner fiber is lost, ciliogenesis and cerebrospinal fluid flow are intact but body axis morphogenesis is impaired. Our results also explain the frequently observed phenotype that mutant embryos with defective cilia exhibit defects in body axis curvature. Here, we reveal that these mutants systematically fail to assemble the Reissner fiber. We show that cilia promote the formation of the Reissner fiber and that the fiber is necessary for proper body axis morphogenesis. Our study sets the stage for future investigations of the mechanisms linking the Reissner fiber to the control of body axis curvature during vertebrate development.

Effects of intra-fourth ventricle injection of crocin on capsaicin-induced orofacial pain in rats.

Crocin, a constituent of saffron and yellow gardenia, possesses anti-nociceptive effects. In the present study, we investigated the effects of intra-fourth ventricle injection of crocin in a rat model of orofacial pain. The contribution of opioid system was assessed using intra-fourth ventricle injection of naloxone, an opioid receptor antagonist. A guide cannula was implanted into the fourth ventricle of brain in anesthetized rats. Orofacial pain was induced by subcutaneous (s.c.) injection of capsaicin (1.5 µg/20 µl) into the right vibrissa pad. The time spent face rubbing/grooming was recorded for a period of 20 min. Locomotor activity was measured using an open-field test. Intra-fourth ventricle injection of crocin (10 and 40 µg/rat) and morphine (10 and 40 µg/rat) and their co-administration (2.5 and 10 µg/rat of each) suppressed capsaicin-induced orofacial pain. The analgesic effect induced by 10 µg/rat of morphine, but not crocin (10 µg/rat), was prevented by 20 µg/rat of naloxone pretreatment. The above-mentioned chemical compounds did not affect locomotor activity. The results of this study showed that the injection of crocin into the cerebral fourth ventricle attenuates capsaicin-induced orofacial pain in rats. The anti-nociceptive effect of crocin was not attributed to the central opioid receptors.

Nesfatin-1 influences the excitability of glucosensing neurons in the dorsal vagal complex and inhibits food intake.

Nesfatin-1 is a recently discovered metabolic peptide hormone that decreases food intake after lateral, third, or fourth brain ventricle; cisterna magna; or paraventricular nucleus (PVN) injection in ad libitum fed rats. Additional micro-injection studies will improve the understanding of how nesfatin-1 acts on the brain and define specific nuclei responsive to nesfatin-1, which will provide insight on its effects on food intake. We evaluated how nesfatin-1 injection into the dorsal vagal complex (DVC) modulates food intake response in rats during the dark phase. Consistent with previous observations, nesfatin-1-injected rats significantly reduced cumulative food intake over a 5-h period in rats. Chronic administration of nesfatin-1 into the DVC reduced body weight gain over a 10-day period. Because glucosensing neurons in the DVC are involved in glucoprivic feeding and homeostatic control of blood glucose, we examined the effect of nesfatin-1 on the excitability of DVC glucosensing neurons. Nesfatin-1 inhibited most of the glucose-inhibitory (GI) neurons and excited most of the glucose-excitatory (GE) neurons in the DVC. Current-clamp electrophysiology recordings from DVC glucosensing neurons in slice preparation showed that bath applied nesfatin-1(10 nM) increased the firing frequency of GE neurons and inhibited the firing rate of GI-neurons. Nesfatin-1 inhibited 88.9% (16/18) of gastric distension inhibitory (GD-INH) neurons and excited 76.2% (32/42) of gastric distension excitatory (GD-EXC) neurons. Thus, nesfatin-1 may control food intake by modulating the excitability of glucosensing neurons in the DVC.

Nesfatin-1 influences the excitability of glucosensing neurons in the hypothalamic nuclei and inhibits the food intake

Nesfatin-1 is a recently discovered neuropeptide that has been shown to decrease food intake after lateral, third, or fourth brain ventricle, cisterna magna administration, or PVN injection in ad libitum fed rats. With regards to the understanding of nesfatin-1 brain sites of action, additional microinjection studies will be necessary to define specific nuclei, in addition to the PVN, responsive to nesfatin-1 to get insight into the differential effects on food intake. In the present study, we evaluated nesfatin-1 action to modulate food intake response upon injection into the specific hypothalamic nuclei (PVN, LHA and VMN) in freely fed rats during the dark phase. We extend previous observations by showing that the nesfatin-1 (50pmol) injected before the onset of the dark period significantly reduced the 1 to 5h cumulative food intake in rats cannulated into the PVN, LHA, but not in rats cannulated into the VMN.Glucosensing neurons located in the hypothalamus are involved in glucoprivic feeding and homeostatic control of blood glucose. In order to shed light on the mechanisms by which nesfatin-1 exerts its satiety-promoting actions, we examined the effect of nesfatin-1 on the excitability of hypothalamic glucosensing neurons. Nesfatin-1 excited most of the glucose-inhibited (GI) neurons and inhibited most of the glucose‐excited (GE) neurons in the PVN. Of 34 GI neurons in the LHA tested, inhibitory effects were seen in 70.6% (24/34) of GI neurons. The main effects were excitatory after intra-VMN administration of nesfatin-1 in GE neurons (27/35, 77.1%). Thus, our data clearly demonstrate that nesfatin-1 may exert at least a part of its physiological actions on the control of food intake as a direct result of its role in modulating the excitability of glucosensing neurons in the PVN, LHA and VMN.

Intravesical pressure (IP) alterations evoked by carbachol into the fourth brain ventricle (4th V) in female rats

Intravesical pressure (IP) alterations evoked by carbachol into the fourth brain ventricle (4th V) in female rats

Coagulation factor III (tissue factor) is required for vascularization in zebrafish embryos

Tissue factor (coagulation factor III) is a cell surface receptor for coagulation factor VII/VIIa; it was initially recognized as an initiator of the extrinsic coagulation pathway. Recently, the zebrafish tissue factor gene (TF) has been cloned. Paralogs encode coagulation factors IIIa and IIIb; both show remarkable sequence identity to the human and mouse coagulation factor III gene. It has been reported that TF could have additional properties that are essential for normal embryonic development, since knockout of the murine coagulation factor III gene resulted in 90% embryonic lethality. We examined the role of coagulation factor IIIb (f3b) during zebrafish embryonic development. Expression analysis revealed that endogenous f3b was chronologically expressed in the pectoral fins and in the vicinity of the pharynx. Knockout of f3b by injection of an f3b morpholino at the one-to-two cell stage caused distinctive morphological defects in embryos, including edema in the fourth brain ventricle at early embryonic stages and occasional bleeding at later stages. Furthermore, f3b morphants displayed abnormal vascular patterning. We conclude that f3b is required for brain vascular development and for development of part of the somatic vasculature during embryogenesis in the zebrafish.

In vivo volumetric imaging of the mouse embryonic brain using chirp-coded excitation and a high-frequency annular-array.

Many genetically engineered mice display abnormal development of the central nervous system (CNS) and high-frequency ultrasound (HFU) offers great potential for efficient, serial in vivo phenotyping of the developing embryonic mouse brain. However, HFU mouse-embryo imaging remains challenging because of the orientation of the embryos and of the limited acoustic penetration depth of HFU. In this study, a 34-MHz, five-element annular array was excited using conventional mono-cycle and chirp-coded excitations. Synthetic focusing and pulse compression (for the chirp excitation) were used to form images with increased depth of field and penetration depth (for the chirp excitation). In utero, in vivo 3-D data sets were acquired from 48 embryos over four stages from embryonic days E10.5 to E13.5, and CNS volume renderings were obtained. The chirp-based renderings were more morphologically accurate than the mono-cycle-based renderings, and the chirp provided sufficient penetration depth to correctly segment the brain ventricles lying deep inside the mother. The chirp renderings indicated that the early CNS architecture was dominated by the third and fourth brain ventricles, with the lateral ventricles contributing more at later stages. [Work supported by NIH Grant nos. NS038461 and EB008606.]

Perioperative observation and nursing of patients with tumor of the fourth brain ventricle

四脑室肿瘤一般指原发自脑室的室管膜、脉络丛的各种肿瘤、囊肿以及由邻近组织长至第四脑室的肿瘤 [1,2],其接近脑干或直接发自四脑室底,位较深,术危险性大,后并发症多,亡率高,科2004年1月-2008年5月共收治四脑室肿瘤患者106例,过对其进行术前、术后的精心护理,手术成功率明显提高,亡率明显下降,报道如下。

Orexin-A Hyperphagia: Hindbrain Participation in Consummatory Feeding Responses

Orexin-A (ORXA) is an orexigenic neuropeptide produced by the lateral hypothalamus that increases food intake when injected into the brain ventricles or forebrain nuclei. We used a licking microstructure analysis to evaluate hindbrain and forebrain ORXA effects in intact and hindbrain-lesioned rats, to identify the motivational and anatomical bases of ORXA hyperphagia. Intact rats with cannulas in the fourth brain ventricle (4V) received vehicle (artificial cerebrospinal fluid) or ORXA (0.1, 0.4, 1, or 10 nm) injections before 90 min access to 0.1 m sucrose. Meal size and frequency were increased in a double-dissociated manner by the 1 and 10 nm doses, respectively. In experiment 2, 4V 1 nm ORXA was applied to rats offered solutions varied in caloric and gustatory intensity (water and 0.1 and 1 m sucrose). ORXA increased meal frequency for all tastants. ORXA increased meal size only for 0.1 m sucrose, by prolonging the meal without affecting early ingestion rate or lick burst size, suggesting that 4V ORXA influenced inhibitory postingestive feedback rather than taste evaluation. In experiment 3, rats with cannulas in the third ventricle (3V) received dorsal medullary lesions centered on the area postrema (APX group) or sham procedures, and licking for water and 0.1 and 1 m sucrose was evaluated after 1 nm 3V ORXA/artificial cerebrospinal fluid injections. The 3V ORXA increased 0.1 m sucrose meal size and meal frequency for all tastants in the sham group, as observed after 4V ORXA in experiment 2. In the APX group, 3V ORXA injections influenced meal frequency, but they no longer increased meal size. However, the APX rats increased meal size for 0.1 m sucrose after food and water deprivation and after 3V angiotensin II injection. They also showed meal size suppression after 3V injection of the melanocortin-3/4 receptor agonist melanotan II (1 nm). These findings suggest that the area postrema and subjacent nucleus of the solitary tract are necessary for increases in consummatory (meal size) but not appetitive (meal frequency) responses to 3V ORXA. The meal size increases may be due to reduced postingestive feedback inhibition induced by ORXA delivered to either the hindbrain or forebrain ventricles.

Goodpasture Antigen-binding Protein and Its Spliced Variant, Ceramide Transfer Protein, Have Different Functions in the Modulation of Apoptosis during Zebrafish Development

Human Goodpasture antigen-binding protein (GPBP) is an atypical protein kinase that phosphorylates the Goodpasture auto-antigen, the alpha3 chain of collagen IV. The COL4A3BP gene is alternatively spliced producing two protein isoforms: GPBP and GPBPDelta26. The latter lacks a serine-rich domain composed of 26 amino acid residues. Both isoforms also function as ceramide transfer proteins (CERT). Here, we explored the function of Gpbp and GpbpDelta26/CERT during embryogenesis in zebrafish. We cloned both splice variants of the zebrafish gene and found that they are differentially expressed during development. We used antisense oligonucleotide-mediated loss-of-function and synthetic mRNA-based gain-of-function approaches. Our results show that the loss-of-function phenotype is linked to cell death, evident primarily in the muscle of the somites, extensive loss of myelinated tracks, and brain edema. These results indicate that disruption of the nonvesicular ceramide transport is detrimental to normal embryonic development of somites and brain because of increased apoptosis. Moreover, this phenotype is mediated by Gpbp but not GpbpDelta26/CERT, suggesting that Gpbp is an important factor for normal skeletal muscle and brain development.

Cardiovascular responses produced by central injection of hydrogen peroxide in conscious rats

Reactive oxygen species (ROS) have been shown to modulate neuronal synaptic transmission and may play a role on the autonomic control of the cardiovascular system. In this study we investigated the effects produced by hydrogen peroxide (H 2O 2) injected alone or combined with the anti-oxidant agent N-acetil- l-cysteine (NAC) or catalase into the fourth brain ventricle (4th V) on mean arterial pressure and heart rate of conscious rats. Moreover the involvement of the autonomic nervous system on the cardiovascular responses to H 2O 2 into the 4th V was also investigated. Male Holtzman rats (280–320 g) with a stainless steel cannula implanted into the 4th V and polyethylene cannulas inserted into the femoral artery and vein were used. Injections of H 2O 2 (0.5, 1.0 and 1.5 μmol/0.2 μL, n = 6) into the 4th V produced transient (for 10 min) dose-dependent pressor responses. The 1.0 and 1.5 μmol doses of H 2O 2 also produced a long lasting bradycardia (at least 24 h with the high dose of H 2O 2). Prior injection of N-acetyl- l-cysteine (250 nmol/1 μL/rat) into the 4th V blockade the pressor response and attenuated the bradycardic response to H 2O 2 (1 μmol/0.5 μL/rat, n = 7) into the 4th V. Intravenous ( i.v.) atropine methyl bromide (1.0 mg/kg, n = 11) abolished the bradycardia but did not affect the pressor response to H 2O 2. Prazosin hydrochloride (1.0 mg/kg, n = 6) i.v. abolished the pressor response but did not affect the bradycardia. The increase in the catalase activity (500 UEA/1 μL/rat injected into the 4th V) also abolished both, pressor and bradycardic responses to H 2O 2. The results suggest that increased ROS availability into 4th V simultaneously activate sympathetic and parasympathetic outflow inducing pressor and bradycardic responses.

Antihypertensive Responses Elicited by Central Moxonidine in Rats: Possible Role of Nitric Oxide

In the present study, we investigated the effects of pretreatment with NG-nitro-L-arginine methyl ester (L-NAME) (nitric oxide synthase inhibitor) injected intravenously (IV) on the hypotension, bradycardia, and vasodilation produced by moxonidine (alpha2-adrenergic/imidazoline receptor agonist) injected into the fourth brain ventricle (4th V) in rats submitted to acute hypertension that results from baroreflex blockade by bilateral injections of kynurenic acid (kyn, glutamatergic receptor antagonist) into the nucleus of the solitary tract (NTS) or in normotensive rats. Male Wistar rats (n=5 to 7/group) anesthetized with IV urethane (1.0 g kg(-1) of body weight) and alpha-chloralose (60 mg kg(-1) of body weight) were used. Bilateral injections of kyn (2.7 nmol 100 nL(-1)) into the NTS increased baseline mean arterial pressure (148 +/- 11 mm Hg, vs. control: 102 +/- 4 mm Hg) and baseline heart rate (417 +/- 11 bpm, vs. control: 379 +/- 6 bpm). Moxonidine (20 nmol microL(-1)) into the 4th V reduced mean arterial pressure and heart rate to similar levels in rats treated with kyn into the NTS (68 +/- 9 mm Hg and 359 +/- 7 bpm) or in control normotensive rats (66 +/- 7 mm Hg and 362 +/- 8 bpm, respectively). The pretreatment with L-NAME (25 micromol kg, IV) attenuated the hypotension produced by moxonidine into the 4th V in rats treated with kyn (104 +/- 6 mm Hg) or in normotensive rats (95 +/- 8 mm Hg), without changing bradycardia. Moxonidine into the 4th V also reduced renal, mesenteric, and hindquarter vascular resistances in rats treated or not with kyn into the NTS and the pretreatment with L-NAME IV reduced these effects of moxonidine. Therefore, these data indicate that nitric oxide mechanisms are involved in hypotension and mesenteric, renal, and hindquarter vasodilation induced by central moxonidine in normotensive and in acute hypertensive rats.

In situ analysis of Raidd-beta-galactosidase fusion gene expression in transgenic mouse midgestation embryos

Apoptosis and differentiation are tightly intertwined processes occurring at organ formation and remodelling during embryonic development. RAIDD (receptor-interacting protein [RIP]-associated ICH-1/CED-3-homologous protein with a death domain), a dual-domain adaptor protein has been shown to mediate the recruitment of CASPASE-2 to tumour necrosis factor receptor-1 (TNF-R1) signalling complex through RIP kinase. However, Raidd overexpression studies suggest that apart from the established role in apoptosis, Raidd may have an additional function in cell differentiation. In this study, we could not generate Raidd null adult mice suggesting that lack of function of Raidd might be embryonic lethal. Thus, to elucidate the role of Raidd during mouse embryogenesis when the processes of organogenesis are most dynamic, we studied the Raidd expression pattern in midgestation mouse embryos. We generated Raidd+/- transgenic mice with a reporter transgene encoding the bacterial Beta-galactosidase (beta-gal) under the control of Raidd promoter. During the midgestation period (E8.5-E12.5), Raidd is expressed in developing organs derived from the ectoderm such as lens, structures of the inner ear and the fourth brain ventricle in regions where differentiation takes place implicating Raidd role in this process. In addition, Raidd expression was found in developing mesenchyme organs like heart and kidney and in the endothelial lining of the midgut at the time when profound morphological changes take place in these organs. In developing heart and kidney Raidd expression patterns overlapped with known zones of cell death suggesting Raidd may be involved in apoptosis-mediated remodelling. The observed lethality of mice targeted at both Raidd alleles and Raidd expression patterns during midgestation period strongly suggest that Raidd plays an important role in mammalian development.

Dopamine D 2 receptors and ingestive behavior: brainstem mediates inhibition of intraoral intake and accumbens mediates aversive taste behavior in male rats

One of the factors that terminate the ingestion of an intraorally infused solution of sucrose may be an increase in the perceived aversiveness of its taste. We tested the hypothesis that dopamine D(2), as opposed to D(1), receptors in the brainstem or nucleus accumbens inhibit intraoral intake by enhancing the aversiveness of the taste of the infused solution. Male rats were infused intraorally with a 2 M sucrose solution (1 ml/min) and intake and the display of gapes and chin rubs, i.e. taste-related aversive behavior, was measured. Gapes and chin rubs were also measured in rats during and 40 s after brief intraoral infusion (1 ml/min during 20 s) of a 0.3 mM solution of quinine HCl. The full D(1) receptor agonist dihydrexidine (0.1-3.0 mg/kg) and antagonist SCH-23390 (0.03-0.1 mg/kg), the D(2) receptor agonist quinpirole (0.3 mg/kg) and antagonist raclopride (1.7 mg/kg) were injected IP. Quinpirole (14-55 microg) and raclopride (5 microg) were also infused into the fourth brain ventricle. In addition, quinpirole (2 or 10 microg) was infused into the shell region of the nucleus accumbens. IP dihydrexidine and quinpirole inhibited the intraoral intake of sucrose and pretreatment with raclopride, but (in the case of dihydrexidine) not SCH-23390, attenuated this effect. Injection of quinpirole into the fourth ventricle produced raclopride-reversible inhibition of intraoral intake but did not stimulate the display of gapes and chin rubs. Infusion of quinpirole into the shell region of the nucleus accumbens had the opposite effects. The intake of sucrose was suppressed by the addition of quinine HCl but this suppression was unaffected by dopamine agonist or antagonist treatment. It is suggested that brainstem dopamine D(2) receptors mediate suppression of consummatory ingestive behavior and that D(2) receptors in the shell region of the nucleus accumbens mediate the display of gapes and chin rubs, but that neither of these D(2) receptor populations mediate the hedonic evaluation of taste.

Blockade of central angiotensin II does not affect the reduction in renal sympathetic nerve activity following a volume load in heart failure rabbits.

1. We investigated the role in sympathetic nerve regulation of endogenous angiotensin (Ang)II in the brain in heart failure by examining the effect of losartan on the resting mean arterial blood pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) and the reflex reduction in RSNA elicited by acute volume expansion in conscious rabbits. 2. Heart failure was induced with doxorubicin (1 mg/kg, i.v., twice weekly for 6 weeks). On the experimental day, MAP, HR and RSNA were recorded in conscious rabbits before and after losartan (10 microg; n = 6) or Ringer's (control; n = 5) injected in the fourth brain ventricle. Animals were then administered an acute volume load with the plasma expander Haemaccel (Hoechst Marion Roussel, Lane Cove, NSW, Australia; 2 mL/min, i.v., for 30 min). 3. Losartan did not significantly affect the resting basal levels of MAP, HR and RSNA. There was no significant difference between losartan- and Ringer's-treated animals. 4. Volume expansion in the control group elicited a significant reduction of 40% in RSNA. In the losartan-treated group, a similar reduction (42%) was observed. There was no significant difference between the treatments. The administration of losartan did not significantly affect MAP and HR during volume expansion compared with the control group. 5. We conclude that AngII in the brainstem does not play a major role in the maintenance of resting MAP, HR and RSNA or in the reflex reduction in RSNA elicited by volume expansion in the conscious rabbit with doxorubicin-induced heart failure.

Role of brain angiotensin II in renal nerve inhibition elicited by volume expansion in the conscious rabbit

Losartan (10 μg/25 μl) or vehicle was injected into the fourth brain ventricle prior to volume expansion (VE) with Haemaccel (2 ml/min for 30 min). RSNA was reduced by a maximum of 45% in response to the VE following vehicle and by 33% following losartan. There was no significant difference between the treatments in RSNA, nor in the blood pressure and heart rate responses. We conclude that endogenous angiotensin II does not make a major contribution to the reflex reduction in RSNA initiated by VE.