Differential effects of intraventricular luteinizing hormone releasing hormone (LH-RH) and norepinephrine on electrical activity of the arcuate nucleus in the proestrous rat

Effects of intraventricular infusions of LH-RH and norepinephrine (NE) on the electrical activity of the arcuate nucleus were investigated in normally cycling proestrous rats. Under urethane anesthesia, recordings were made of amplitude-discriminated multiple unit spike activity and integated multiunit activity (MUA) in parallel with cortical EEG. Control infusions of saline (2 microliter, isotonic, pH 5.5) were ineffectual, but LH-RH (0.5 microgram) induced a significant increase in both multiunit spike activity and integrated MUA. While the response appeared to be continuous, statistical analysis revealed 2 phases: a quick rise which persisted for approximately 5 min, followed 15 min later by a longer-lasting elevation in activity. The onset of the 2nd increase corresponded with the attainment of peak values of pituitary LH output. Subsequent treatment with 20 microgram NE, on the other hand, resulted in a marked depression of activity. The fact that NE depresses arcuate neuronal activity at dose levels which cause the release of LH and that LH-RH increases activity within the same population of neurons, while possibly mediating an 'ultrashort-loop' negative feedback effect, suggest that this responsive component of the arcuate nucleus, perphaps the tuberoinfundibular dopaminergic system of neurons, is inhibitory to LH release.     

L-Cysteinesulfinic acid modulates cardiovascular function in the periaqueductal gray area of rat

L-Cysteinesulfinic acid (CSA) involvement in modulating periaqueductal gray (PAG) pressor neurons has been evaluated in the rat. Intra-PAG CSA induced an increase in mean blood pressure partially antagonized by (2S)-alpha-ethylglutamic acid (EGA), a group II metabotropic glutamate receptors (mGluRs) antagonist. Conversely, the NMDA antagonist, DL-AP5, or the mGluRs antagonists, (+)-MCPG, UPF523, or (RS)-alpha-methylserine-O-phosphate (MSOP), were devoid of any activity on the CSA effect. These data show that the excitatory amino acid CSA, probably by stimulating an mGluR, contributes with glutamate in modulating cardiovascular function at the PAG matter.     

Cardiovascular effects of microinjections of opioid agonists into the ''Depressor Region'' of the ventrolateral periaqueductal gray region

Differentiating the binding properties of applied lectins should facilitate the selection of lectins for characterization of glycoreceptors on the cell surface. Based on the binding specificities studied by inhibition assays of lectin-glycan interactions, over twenty Gal and/or GalNAc specific lectins have been divided into eight groups according to their specificity for structural units (lectin determinants), which are the disaccharide as all or part of the determinants and of GalNAc alpha 1-->Ser (Thr) of the peptide chain. A scheme of codes for lectin determinants is illustrated as follows: (1) F (GalNAc alpha 1-->3GalNAc), Forssman specific disaccharide--Dolichos biflorus (DBL), Helix pomatia (HPL) and Wistaria floribunda (WFL) lectins. (2) A (GalNAc alpha 1-->3 Gal), blood group A specific disaccharide--Codium fragile subspecies tomentosoides (CFT), Soy bean (SBL), Vicia villosa-A4 (VVL-A4), and Wistaria floribunda (WFL) lectins. (3) Tn (GalNAc alpha 1-->Ser (Thr) of the protein core)--Vicia villosa B4 (VVL-B4), Salvia sclarea (SSL), Maclura pomifera (MPL), Bauhinia purpurea alba (BPL) and Artocarpus integrifolia (Jacalin, AIL). (4) T (Gal beta 1-->3GalNAc), the mucin type sugar sequences on the human erythrocyte membrane(T alpha), T antigen or the disaccharides at the terminal nonreducing end of gangliosides (T beta)--Peanut (PNA), Bauhinia purpurea alba (BPL), Maclura pomifera (MPL), Sophora japonica (SJL), Artocarpus lakoocha (Artocarpin) lectins and Abrus precatorius agglutinin (APA).(5) I and II (Gal beta 1-->3(4)GlcNAc)--the disaccharide residue at the nonreducing end of the carbohydrate chains derived from either N- or O-glycosidic linkage--Ricinus communis agglutinin (RCA1), Datura stramonium (TAL, Thorn apple), Erythrina cristagalli (ECL, Coral tree), and Geodia cydonium (GCL). (6) B (Gal alpha 1-->3Gal), human blood group B specific disaccharide--Griffonia(Banderiaea) simplicifolia B4 (GSI-B4). (7) E (Gal alpha 1-->4Gal), receptors for pathogenic E. coli agglutinin, Shiga toxin and Mistletoe toxic lectin-I (ML-I) and abrin-a.     

Release of renal kallikrein to the perfusate by isolated rat kidney

The addition of furosemide to the fluid used to perfuse isolated rat kidney increases the kallikrein activity found in the perfusion fluid. The experiments favour the concept that furosemide activates a kallikrein precursor or/and the synthesis and release of kallikrein in the kidneys.     

Synaptic effects of nitric oxide on enkephalinergic, GABAergic, and glutamatergic networks of the rat periaqueductal gray

Previous studies have shown that the injection of nitric oxide (NO) donating compounds into the dorsal periaqueductal gray region of the midbrain (PAG) decreases mean arterial pressure (MAP), while the injection of NO synthase (NOS) inhibitors increases MAP. In this study we used both in-vivo and in-vitro preparations and examined the effect of a NO donor and a NOS inhibitor on MAP, membrane properties, and synaptic activities in PAG neurons. We found that: (1) Injection of the NO donor hydroxylamine (HA) into the dorsal PAG decreased MAP, while the injection of the neuronal NOS (nNOS) inhibitor, 1-(2-trifluoromethylphenyl) imidazole (TRIM) increased MAP. These responses were consistent and site-specific. (2) HA-evoked hypotensive responses were mediated by PAG neuronal activity, because they were blocked by pre-injection with gamma-amino-butyric acid (GABA). (3) HA consistently increased the rate of observable synaptic events while TRIM consistently decreased the rate of observable synaptic events. (4) Bicuculline (BIC) and naloxone (NAL) blocked HA-evoked increases in the rate of observable inhibitory synaptic events. (5) Perfusion with sodium nitroprusside (SNP) and illumination with bright light consistently elevated rates of observable synaptic events, and SNP-evoked increases of excitatory synaptic events were blocked by pretreatment with glutamic acid antagonists. (6) PAG-medullary projecting neurons exhibited similar response patterns. The results of this study suggest that: (1) NO production within the PAG is a major component of PAG-mediated cardiovascular responses. (2) The effects of NO may be mediated in part by increased presynaptic vesicular release of glutamic acid, GABA, and enkephalin.     

Occlusion of the femoral artery induced fos-like immunoreactive neurons in the lateral habenular nucleus projecting to the midbrain periaqueductal gray in the rat

BACKGROUND: Inactivated hepatitis A vaccines are licensed with a vaccination schedule based on two injections of vaccine given at least 6 months apart. METHODS: Two vaccination schedules for the inactivated hepatitis A vaccine, AvaximTM (Pasteur Mérieux Connaught, Lyon, France), were compared in a monocentric, randomized, open trial. Two doses of the vaccine were given at intervals of either 6 months (0-6 month group) or 12 months (0-12 month group) to 96 adult volunteers. Anti-hepatitis A virus (HAV) antibody titers were determined in a blind fashion using the modified RIA (mRIA) HAVABtrade mark assay. After excluding subjects with positive preimmunization anti-HAV titers and those with protocol deviations, both groups were still comparable by sex ratio and mean age. RESULTS: Four weeks (28 6 4 days) after the first dose, the seroconversion (SC) rate of initially HAV-seronegative subjects (antibody titer < 20 mIU/mL) was 100% in the 0-6 month group and 96. 9% in the 0-12 month group, with corresponding geometric mean titer (GMT) values (95% CI) of 369 mIU/mL (274-497 mIU/mL) and 445 mIU/mL (292-679 mIU/mL), respectively. After 6 months, SC was obtained in all subjects, and the corresponding GMT values were 349 mIU/mL and 359 mIU/mL in the 0-6 month group and the 0-12 month group, respectively. Four weeks after the booster dose given at 6 months, a 14.5-fold rise in GMT was observed. In the 0-12 month group, anti-HAV GMT values decreased by only 20% from 6 months to 12 months with a pre-booster GMT value of 286 mIU/mL at the 12-month evaluation. Four weeks after the booster given at 12 months, a 22. 5-fold rise in GMT was observed. Statistical analysis showed that the two vaccination schedules were comparable in their ability to boost antibody titers. Unsolicited reactions to vaccination were not different to those reported during earlier trials. Less than 12% of the vaccinees reported reactions after the first dose (11/93), or after the booster dose (11/92). CONCLUSIONS: This trial demonstrated antibody persistence is excellent for at least 12 months after one dose of this vaccine, and that a booster may be given at any time between 6 and 12 months after primary immunization.     

Inhibitory effects of hypothalamic arcuate nucleus or anterior pituitary stimulation on the nociceptive responses of thalamic parafascicular neurons

The effects of hypothalamic arcuate nucleus (ARC) or anterior lobe of pituitary (AL) stimulation on the nociceptive responses of thalamic parafascicular (Pf) neurons were studied in rats with electrophysiological technique. The results showed that ARC stimulation could inhibit the nociceptive discharges of Pf neurons, namely, the immediate inhibition because of its very short latency and duration. AL stimulation could also inhibit the nociceptive discharges of Pf neurons, but this inhibition was a delayed one because of its longer latency and duration. Hypophysectomy diminished the immediate inhibition due to ARC stimulation, while ARC lesion diminished the delayed inhibition due to AL stimulation. Both kinds of inhibition were blocked by dexamethasone pretreatment. The above results suggest that neuroendocrine relationship between ARC and AL is involved in pain modulation.     

Stereotyped yawning responses induced by electrical and chemical stimulation of paraventricular nucleus of the rat

Yawning was evoked by electrical or chemical stimulation in the paraventricular nucleus (PVN) of anesthetized, spontaneously breathing rats. To evaluate physiological aspects of yawning, we monitored polygraphic measures as follows; a coordinated motor pattern of yawning was assessed by monitoring breathing [intercostal electromyogram (EMG)], mouth opening (digastric EMG), and stretching of the trunk (back EMG). We also recorded blood pressure (BP), heart rate, and the electrocorticogram (ECoG) to evaluate autonomic function and arousal responses during yawning. A stereotyped yawning response was reproducibly evoked by electrical stimulation or microinjection of -glutamate or NOC-7, a nitric oxide (NO)-releasing compound, into the PVN. The stereotyped yawning response consisted of two sequential events, an initial response represented a depressor response and an arousal shift in the ECoG to lower voltage and faster rhythms. These initial changes were followed by a yawning behavior characterized by a single large inspiration with mouth opening and stretching of the trunk. A similar sequence of events occurred during spontaneous yawning; a fall in BP and ECoG arousal preceded a yawning behavior. An increase in the frequency of spontaneous yawns was also observed after microinjection of -glutamate or NOC-7 into the PVN. Intravenous administration of NG-monomethyl--arginine, an inhibitor of nitric oxide synthase (NOS), prevented the stereotyped yawning response evoked by chemical stimulation of the PVN. Histological examination revealed that effective sites for the yawning responses were located in the medial part of the rostral PVN, the site of parvocellular and magnocellular neurons. NADPH-diaphorase histochemistry showed the existence of NOS-containing cells in yawning-evoked sites of the PVN. In summary, the sequential events of yawning may be generated by NOS-containing parvocellular neurons in the medial part of the rostral PVN projecting to the lower brain stem.     

Systematic examination in the rat of brain sites sensitive to the direct application of morphine: observation of differential effects within the periaqueductal gray

An extensive mapping of the rat brain (403 sites) ranging from AP +8 to AP -3 revealed that the region showing maximum sensitivity to the intracerebral administration of morphine in the elevation of the nociceptive threshold lay within the periaqueductal gray. Analysis of the distribution of responsive sites indicated that the most active sites, those having the shortest latency of effect, were located within the ventrolateral aspect of the caudal periaqueductal gray. These antinociceptive actions of morphine were observed to be both dose-dependent and reversible by the administration of naloxone. We observed that microinjections of morphine could produce changes in the pinch withdrawal response which were distributed in a crude somatotopic fashion. Injections into the rostral aspect of the periaqueductal gray yielded a block of the pinch response in the rostral portions of the body, whereas such injections into the caudal periaqueductal gray always yielded a whole body analgesia. In the rostral sites, transient ipsilateral blocks of the pinch response were occasionally seen. A pinch block limited to the hind paws alone was never observed. It is suggested that morphine acting through the periaqueductal gray may actuate a potent supraspinal modulatory system related to the transmission of information derived from behaviorally aversive stimuli.     

Immunocytochemical localization of substance P receptor in rat periaqueductal gray matter: a light and electron microscopic study

The distribution of substance P receptor (SPR) protein in the rat periaqueductal gray matter (PAG) was investigated with a polyclonal antibody in the four subdivisions obtained by cytochrome-oxidase histochemistry (Co-hi). At light microscopic analysis, immunoreactivity appeared particularly dense in the dorsal subdivision of the PAG, was less intense in the other subdivisions, and formed several longitudinally organized columns. SPR-like immunoreactivity (SP(R-i)) was localized mostly to cell bodies and dendrites of small and medium-sized neurons, which constituted about 6% of the total neuronal population of the PAG. At the electron microscopic level, SP(R-i) could be observed on postsynaptic as well as on nonsynaptic regions of both cell bodies and dendrites. A small proportion of axons (4.2%) and axon terminals (5.3%) showed SP(R-i), the majority of labeled axon terminals, amounting to about 70% of synapsing elements, formed asymmetric synapses with dendrites. Rare astroglial processes displaying SP(R-i) were also observed scattered throughout the neuropil of all PAG subdivisions. Our observations suggest that 1) also in the PAG, SP may act in a diffuse, nonsynaptic manner, probably on targets that are distant from its sites of release; and 2) SP may modulate excitatory neurotransmission acting presynaptically on those labeled axons that form asymmetric synapses.     

The role of corticosteroids in analgesic effect caused by stimulation of the periaqueductal gray matter of the midbrain in rats

The effects of stimulation of periaqueductal gray matter on pain threshold and blood corticosterone level were studied in anesthetized rats. The stimulation resulted in a alteration of analgesia and corticosterone level. Stimuli-induced analgesia was decreased by adrenalectomy. Corticosterone implantation (50 micrograms) in periaqueductal gray matter resulted in the increase of analgesia. Pretreatment with naloxone (1 mg/kg) failed to modify the effect of stimulation of periaqueductal gray matter on analgesia and corticosterone level. Our results indicate the involvement of corticosterone in the analgesia induced the stimulation of periaqueductal gray matter.     

Amygdaloid–thalamic interactions mediate the antinociceptive action of morphine microinjected into the periaqueductal gray.

The bilateral administration of the serotonin receptor antagonist methysergide (2.5 μg, 5 μg, and 10 μg) into either the central nucleus of the amygdala (ACe) or nucleus parafascicularis thalami (nPf) produced dose-dependent inhibition of the antinociceptive action of ventrolateral periaqueductal gray (vPAG)-administered morphine. Unilateral administration of these doses of methysergide into either the ACe or nPf had no effect on morphine-induced antinociception. However, the combined unilateral administration of these doses of methysergide into the ACe and nPf produced dose-dependent inhibition of morphine antinociception that was identical to that observed after its bilateral administration into either site. This latter finding is interpreted as evidence that a functional interaction between the ACe and nPf supports the antinociceptive action of morphine administered into the vPAG. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of hypothalamic paraventricular nucleus: electrical stimulation produce marked analgesia in rats

The effect of the electrical simulation induced analgesia (ESIA) on the hypothalamic paraventricular nucleus (PVN) was investigated by the paw pressure test, which was used to avoid any tissue damage to the paw of Wistar-SPF/VAF male rats. A stimulating electrode was chronically implanted in the parvocellular (PVN-prv) or magnocellular (PVN-mgn) divisions of the PVN. The ESIA was examined at least 10 days after surgery. The electrical stimulation of the PVN markedly showed analgesia (ESIA), but stimulation of most locations outside the PVN did not produce ESIA. Stimulation threshold for the ESIA was lower from PVN-prv than from PVN-mgn, but neither region was affected by naloxone administration (10 mg/kg, i.p.). These results indicate that the PVN is a part of the pain inhibitory system in the CNS, and show that PVN-ESIA might not be mediated either by opioids or by neuropeptides such as vasopressin.     

The effects of electrical stimulation of the nucleus basalis on the electroencephalogram, heart rate, and respiration.

The nucleus basalis (NB) mediates cortical electroencephalograph (EEG) activation; NB stimulation also modulates cortical responses to sensory stimuli and can induce learning-related receptive field plasticity. However, little is known about the behavioral effects of NB stimulation. This study concerns the effects of NB stimulation on cardiac and respiratory behavior and quantifies its EEG effects in freely moving rats. The EEG exhibited stimulation-induced decreases in theta and alpha power and increases in gamma power. NB stimulation elicited biphasic heart rate changes and disrupted ongoing respiration patterns. Neither EEG nor behavioral effects exhibited habituation or facilitation. These results indicate that the NB may serve not only as a cortical, but also as a behavioral, activation system that is normally engaged during learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Shock-induced hyperalgesia: II. Role of the dorsolateral periaqueductal gray.

Exposure to 3 moderately intense (1-mA) tailshocks has been shown to lower vocalization thresholds to both heat and shock. Previous shock exposure also facilitates the acquisition of conditioned fear as measured by freezing. These observations suggest that shock induces hyperalgesia (enhanced pain). This study explored whether shock-induced hyperalgesia depends on neurons within rostral or caudal portions of the dorsolateral periaqueductal gray (dlPAG). Experiment 1 examined the impact of dlPAG lesions on the acquisition of conditioned fear. Sham-operated rats demonstrated enhanced acquisition after shock exposure; both rostral and caudal lesions eliminated this effect. Experiment 2 showed that tailshock lowered vocalization thresholds to heat in sham-operated but not lesioned subjects. These results suggest that the dlPAG plays a critical role in the production of shock-induced hyperalgesia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Opposing roles of the amygdala and dorsolateral periaqueductal gray in fear-potentiated startle

The whole-body acoustic startle response is a short-latency reflex mediated by a relatively simple neural circuit in the lower brainstem and spinal cord. The amplitude of this reflex is markedly enhanced by moderate fear levels, and less effectively increased by higher fear levels. Extensive evidence indicates that the amygdala plays a key role in the potentiation of startle by moderate fear. More recent evidence suggests that the periaqueductal gray is involved in the loss of potentiated startle at higher levels of fear. The influence of both structures may be mediated by anatomical connections with the acoustic startle circuit, perhaps at the level of the nucleus reticularis pontis caudalis. The present chapter reviews these data.     

Inhibitory effects of acupuncture manipulation and focal electrical stimulation of the nucleus submedius on a viscerosomatic reflex in anesthetized rats

To examine the participation of nucleus submedius (Sm) in the medial thalamus of pain inhibitory systems, we investigated the effects of acupuncture and focal electrical stimulation of the Sm and adjacent brain sites (0.3 ms, 50 Hz, 50-100 microA, 10 s) on the EMG activity of the external oblique muscle evoked by colorectal distension in urethane-anesthetized Wistar rats. The viscerosomatic reflex (VSR) activity was suppressed after the administration of morphine (1.0 mg/kg, i.v.) and the effect was reversed by naloxone (0.5 mg/kg, i.v.). Transection of the spinal cord at the Th2 level also eliminated the VSR. Acupuncture manipulation applied to the cheek (manual rotation at 1 Hz) suppressed the VSR, and this inhibition was eliminated by microinjections of lidocaine into the bilateral Sm nuclei (0.5 microliter of 1.0% solution). Electrical stimulation in the ventral part but not the dorsal part of the Sm suppressed the VSR. The inhibition of the VSR induced by electrical stimulation of the Sm was not reversed by the administration of naloxone (1.0 mg/kg, i.v.). Electrical stimulation of the adjacent medial thalamic nuclei (mediodorsal nucleus (MD) or centromedial nucleus (CM)) and ventrobasal complex (VB) of the thalamus had very little effect on the VSR. These results suggests that the Sm is not only involved in the relay of nociceptive information to the cortex, but may also be involved in a non-opioid mediated pain inhibitory system and may participate, at least in part, in the suppressive effects of intense acupuncture manipulation on VSR activity.     

Extensive projections from the midbrain periaqueductal gray to the caudal ventrolateral medulla: a retrograde and anterograde tracing study in the rat

We investigated the innervation of the caudal ventrolateral medulla by the midbrain periaqueductal gray in the rat using retrograde and anterograde tract-tracing. Iontophoretic injection of Fluoro-Gold or cholera toxin B subunit into the caudal ventrolateral medulla resulted in retrogradely labeled neurons in discrete regions of the periaqueductal gray. These labeled cells were observed throughout the rostrocaudal extent of the periaqueductal gray and were distributed (as percentage of total labeled cells) in its lateral (53-67%), ventrolateral (14-28%), ventromedial (7-16%) and dorsomedial aspects (7-10%). About 70-72% of labeled cells were found in the caudal half of the periaqueductal gray and 28-30% in the rostral half. In the ventromedial periaqueductal gray, more labeled cells were seen in the contralateral side (5-13%) than the ipsilateral side (2-3%), whereas for other periaqueductal gray areas labeling was preferentially ipsilateral. Phaseolus vulgaris leucoagglutinin anterograde tracing was used to confirm the retrograde labeling results. Following iontophoretic injection into the periaqueductal gray, labeled fibers and terminals were observed throughout the rostrocaudal extent of the caudal ventrolateral medulla. Injections in the lateral and/or ventrolateral aspect of the periaqueductal gray yielded more anterograde labeling in the ipsilateral than the contralateral caudal ventrolateral medulla, while injections in the ventromedial aspect of the periaqueductal gray produced labeling preferentially in the contralateral caudal ventrolateral medulla. The present study indicates that specific regions of the periaqueductal gray project to the caudal ventrolateral medulla and may regulate cardiovascular and respiratory functions through these connections.