Somatotopic and laminar organization of fos-like immunoreactivity in the medullary and upper cervical dorsal horn induced by noxious facial stimulation in the rat

The distribution of fos-like-immunoreactivity (fos-LI) in the medullary and upper cervical dorsal horn was examined following noxious facial stimulation, in order to evaluate the use of fos as a marker for neuronal activation in trigeminal nociceptive pathways. Control animals that received urethane anesthesia and no facial stimulation showed substantial bilateral labeling in the trigeminal complex that was restricted to one rostrocaudal level, at the transition between the medullary dorsal horn (nucleus caudalis) and nucleus interpolaris. Noxious mechanical stimulation (pinch) of different facial sites produced labeling in the ipsilateral dorsal horn whose distribution varied predictably with the rostrocaudal and dorsoventral position of the facial stimulation site, such that rostral facial sites were represented rostrally in the dorsal horn and dorsal sites were represented ventrolaterally. The cornea was exceptional among the facial stimulation sites in that it had a specific representation at two distinct rostrocaudal levels, in C1 and the interpolaris-caudalis transition region; the position of the rostral peak was somatotopically inappropriate, based on the representation of other facial sites. The proportion of labelling in laminae III-IV relative to laminae I-II was higher with noxious mechanical stimulation than with noxious thermal (55 degrees C) or chemical (subcutaneous injection of capsaicin) stimulation. The proportion of labelling in laminae III-IV produced by electrical stimulation of the infraorbital nerve was no greater than that produced by pinch. The results suggest that fos-LI mapping can be a useful method for the investigation of somatotopy but is subject to serious limitations when used for the investigation of laminar organization. The results also suggest that the interpolaris-caudalis transition region may have properties that are distinct from those of the rest of the trigeminal complex, possibly related to an involvement in autonomic function.     

Peripheral and central contributions to the persistent expression of spinal cord fos-like immunoreactivity produced by sciatic nerve transection in the rat

In the absence of reliable baseline data for normal neuron density in the intestine, the diagnosis of hypo- and hyperganglionosis is purely subjective. This study has established the normal neuron density by neuron counts in paraffin sections taken both transversely (transverse sections, TS) and longitudinally (longitudinally sections, LS) in relation to the long axis of normal postmortem jejunum, ileum, and colon from 21 children (aged 4 weeks to 10 years). Intestine from two adults (aged 16 and 42 years) and colon alone from a further six adults (aged 16 to 83 years) were also studied. The mean density values in childhood were for jejunum 3.6/mm (TS), 3.7/mm (LS); for ileum 4.3/mm (TS, LS); and for colon 7/mm (LS), 7.7/mm (TS). The proximal margins of surgically resected colons from six patients with Hirschsprung's disease and one patient with suspected isolated hypoganglionosis were also analyzed and the neuron densities compared with the established postmortem data. Neuron density values outside two standard deviations from the postmortem mean were shown to correlate with continuing pseudo-obstructive symptoms in these patients.     

Electromyographic analysis of the ingestion and rejection of sapid stimuli in the rat.

For further clarification of the relation between orofacial movements produced by gustatory stimuli (the buccal phase of ingestion) and the act of swallowing (the pharyngeal phase), electromyogram (EMG) responses to intraoral sapid stimulation were recorded from a subset of orofacial and pharyngeal muscles in 25 male rats. Muscle activity reliably differentiated between ingestive sequences to water (W), sucrose (S), and NaCl (N) and a rejection response elicited by quinine monohydrochloride (Q). Ingestion responses to W, S, and N consisted of rhythmic alternations between genioglossus and styloglossus activity (intraoral licks) accompanied by episodic bursts of pharyngeal constrictor activity (swallowing). Both bout duration and number of swallows increased at higher concentrations of S and N. In contrast, Q stimulation elicited a rejection response characterized by several licks and followed by long duration contractions of the zygomatic and anterior digastric muscles (gapes). During gapes, styloglossus activity rather than genioglossus activity was simultaneous with that of the anterior digastric. At higher concentrations of Q, the latency to gape decreased and the latency to swallow increased. The earliest components of the response to S, N, or Q were indistinguishable from one another, suggesting that tactile (fluid) stimulation initiates the ingestive sequence and that gustatory stimuli modulate this ongoing activity. (49 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The medullary reticular formation is a site of muscle relaxant action of diazepam on deep back and neck muscles in the female rat

We tested the hypothesis that the effect of systemic injections of diazepam (DZ, 125 mg/kg) to reduce the quality of the reproductive behavior, lordosis, and to reduce the EMG of lumbar back muscles involved in lordosis (Schwartz-Giblin et al., 1984) is exerted through a reticulospinal pathway with cells of origin in the nucleus gigantocellularis that excites lumbar motoneurons indirectly (Robbins et al., 1990, Robbins et al., 1992). In contrast, DZ facilitates lordosis behavior when infused into the midbrain central gray (McCarthy et al., 1995). Direct deposits of crystalline mixtures of DZ (20-80 ng) in dextrose were delivered to the medullary reticular formation (MRF) by diffusion from a cannula inserted through a guide to which a bipolar stimulating electrode was attached. The multiunit EMG response evoked by 20 (300 ms long) stimulus trains was recorded in back and neck muscles, lateral longissimus and splenius before and 5, 15, 30 and 60 min after local DZ deposits. There was a significant reduction in EMG response over this time period when stimulus intensities were within the range of 1.2-1.5 times threshold (Friedman two-way non-parametric test, P < 0.002). Large amplitude motor units that provide large tensions were the most sensitive to DZ-induced inhibition. Control deposits of dextrose had no significant effect. Systemic injections of progesterone (1 mg, i.p.) 60 min after DZ deposits, but not after dextrose deposits, further reduced the MRF-evoked EMG responses over the course of 1 h. As predicted, DZ infusions into the midbrain central gray did not reduce the reticulospinal-evoked axial muscle response, consistent with the facilitatory effect of midbrain central gray infusions of DZ on the lordosis quotient. The results suggest that benzodiazepine agonists (if endogenous) acting at sites in the MRF would be effective muscle relaxants during pregnancy, prior to the fall in progesterone that precedes labor.     

The medullary dorsal reticular nucleus facilitates pain behaviour induced by formalin in the rat

The influence of the dorsal reticular nucleus (DRt) on pain behaviour during the formalin test was studied in the rat by lesioning the nucleus through local application of electrical current or quinolinic acid. Animals in which the DRt was lesioned ipsilaterally to the paw injected with formalin spent less time in focused (licking, biting or scratching the injected paw) and total (focused pain behaviour plus protection of the injected paw during movements) pain behaviour, and showed paw-jerks less frequently than non-lesioned animals in both phases 1 and 2 of the test. Animals in which the DRt was lesioned contralaterally to the injected paw presented a decrease in total pain behaviour and number of paw-jerks only during phase 2. The number of superficial (laminae I-II) and deep (laminae III-VI) spinal dorsal horn cells expressing the c-fos proto-oncogene 2 h after subcutaneous injection of formalin was reduced by 34% and 50%, respectively, in animals with an ipsilateral DRt lesion as compared to non-lesioned rats. No differences in c-fos expression were observed after lesioning the DRt contralateral to the formalin injection. The results indicate that the DRt is involved in the facilitation of nociception during the formalin test by enhancing the response capacity of dorsal horn neurons to noxious stimulation. It is suggested that the pronociceptive action of the DRt is mediated by the reciprocal connections it establishes with the spinal dorsal horn.     

The involvement of medullary reticular formation in the hypotensive effect of extracts from seeds of Cassia tora

In pentobarbital anesthetized rats, the medial portion of the medullary reticular formation has been identified to be directly involved in the hypotensive effect of extracts from the seeds of Cassia tora. This conclusion was drawn from the observed decrease in arterial blood pressure following local injection of extracts of this herb into this reticular site and from its inability to promote hypotension when the same reticular site has been electrolytically lesioned. The role of the medullary reticular formation in the Cassia tora-induced hypotension was suggested to be one which modulates the basic cardiovascular reflexes, favoring a decrease in vasomotor tone.     

Distribution of trigeminothalamic and spinothalamic-tract neurons showing substance P receptor-like immunoreactivity in the rat

Trigeminothalamic and spinothalamic-tract neurons provided with substance P receptor (SPR) were examined in the rat by SPR immunofluorescence histochemistry combined with Fluoro-Gold (FG) fluorescent retrograde labeling. After FG injection in the thalamic regions, FG-labeled cells with SPR-like immunoreactivity were seen mainly in laminae I and III of the medullary and spinal dorsal horns and lateral spinal nucleus. In these regions, about one-fourth to one-third of FG-labeled cells showed SPR-like immunoreactivity.     

Effects of sympathetic inhibition on receptive, proceptive, and rejection behaviors in the female rat

The present investigation was designed to examine the effects of sympathetic nervous system (SNS) inhibition on sexual behavior in ovariectomized, steroid-treated female rats. Clonidine, an alpha2-adrenergic agonist, guanethidine, a postganglionic noradrenergic blocker, and naphazoline, an alpha2-adrenoreceptor agonist were used to inhibit SNS activity. Intraperitoneal injections of either 33 micrograms/ml or 66 micrograms/ml clonidine significantly decreased receptive (lordosis) and proceptive (ear wiggles) behaviors and significantly increased rejection behaviors (vocalization, kicking, boxing). Either 25 mg/ml or 50 mg/ml guanethidine significantly decreased receptive and proceptive behavior and had no significant effect on rejection behaviors. Naphazoline significantly inhibited lordosis behavior at either 5 mg/ml or 10 mg/ml doses, significantly inhibited proceptive behavior at 5 mg/ml, and had no significant effect on rejection behaviors. These findings support the hypothesis that SNS inhibition decreases sexual activity in the female rat.     

Neuroanatomical patterns of fos-like immunoreactivity induced by a palatable meal and meal-paired environment in saline- and naltrexone-treated rats

Opioid antagonists block the positive hedonic response to food taste and are potent inhibitors of palatability-driven feeding. However, the specific brain regions within which opioid peptide secretion contributes to the maintenance of palatability-driven feeding have not been clearly established. In the present study, c-Fos immunohistochemistry was used to identify regions rostral to the hindbrain that display cellular activation in response to a palatable meal and the meal-paired environment. Further, it was determined whether any of the cellular responses could be prevented by pretreating animals with naltrexone. Twenty brain regions known to be involved in gustation, appetite and reward functions were examined. Ingestion of the palatable meal (3.0 g of 30% shortening, 20% sucrose and 50% powdered Purina rat chow) increased Fos-like immunoreactivity (FLI) in lateral hypothalamus (LH), ventral tegmentum (VTA) and medial preoptic area (MPOA), and decreased FLI in the habenula (Hab). The meal-paired environment increased FLI in the VTA and nucleus accumbens shell (NAC shell). Naltrexone (1.0 mg/kg, i.p.) did not block consumption of the small meal but did prevent all of the distinctive increases in FLI induced by the meal and meal-paired environment. Since naltrexone, alone, increased FLI in VTA, NAC shell, central amygdala (ceA) and laterodorsal bed nucleus of the stria terminalis (BSTLD), the blunting of ingestion reward by naltrexone may result from direct or transsynaptic activating effects on opponent neuronal activity within this highly interconnected set of structures that mediate and modulate reward.     

Distribution of trigeminohypothalamic and spinohypothalamic tract neurons displaying substance P receptor-like immunoreactivity in the rat

Primary afferent neurons containing substance P (SP) are apparently implicated in the transmission of noxious information from the periphery to the central nervous system, and SP released from primary afferent neurons acts on second-order neurons with the SP receptor (SPR). In the rat, nociceptive information reached the hypothalamus not only through indirect pathways but also directly through trigeminohypothalamic and spinohypothalamic pathways. Thus, in the present study, the distribution pattern of trigeminohypothalamic and spinohypothalamic tract neurons showing SPR-like immunoreactivity (SPR-LI) was examined in the rat by a retrograde tract-tracing method combined with immunofluorescence histochemistry for SPR. A substantial number of trigeminal and spinal neurons with SPR-LI were retrogradely labeled with Fluoro-Gold (FG) injected into the hypothalamic regions. These neurons were distributed mainly in lamina I of the medullary and spinal dorsal horns, lateral spinal nucleus, regions around the central canal of the spinal cord, and the lateral aspect of the deep part of the spinal dorsal horn. A number of SPR-LI neurons in the spinal parasympathetic nucleus were labeled with FG injected into the area around the paraventricular hypothalamic nucleus. Some SPR-LI neurons in the lateral spinal nucleus and the lateral aspect of the deep part of the spinal dorsal horn were also labeled with FG injected into the septal region. On the basis of the distribution areas of SPR-LI trigeminal and spinal neurons projecting to the hypothalamic and septal regions, it is likely that these neurons are involved in the transmission of somatic and/or visceral noxious information.     

Localization of endothelin-like immunoreactivity in the hypothalamo-neurohypophysial system of the rat after ischemia

Endothelin is a very powerful endogenous vasoconstrictor substance produced by endothelial cells. To examine the potential role of endothelin as a neuropeptide, we studied its distribution in the neurosecretory system. Endothelin-like immunoreactivity (EN-IR) has been demonstrated by an immunogold method in the paraventricular and supraoptic nuclear neurons and their terminals in the posterior pituitary of the rat. ET-IR was enhanced after ischemia suggesting its modulatory role in neurosecretory functions.     

Effects of mesencephalic reticular formation lesions on habituation of startle and lick suppression responses in the rat.

In 2 experiments with 43 male albino Holtzman rats, extensive damage to the mesencephalic reticular formation (MRF) altered long-term habituation of the acoustic startle response without disrupting short-term habituation. Ss with MRF lesions, although initially neither more nor less responsive than controls, could not attain as low a long-term asymptote of habituation as could control Ss with repeated presentations of an auditory stimulus. Changing the quality of the auditory stimulus abolished the asymptotic difference in responsiveness. With repeated presentations of the 2nd auditory stimulus, control Ss again reached a significantly lower long-term habituation asymptote than did Ss with MRF lesions. The course of long-term habituation for the 2 groups suggested a disruption of an extrinsic, inhibitory habituation process by the lesions. The effects of MRF lesions were specific to the acoustic startle response. Control Ss and those with lesions showed comparable response levels, short-term habituation, and long-term habituation of the lick suppression response. Responsiveness and habituation to tactile stimuli were comparable for the 2 groups on both lick suppression and startle response measures. (32 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Facilitation of flicker discriminability by electrical stimulation of the mesencephalic reticular formation of the rat.

In 4 experiments with 23 male Sprague-Dawley rats, low-intensity, 7 and 10 μA, electrical stimulation of the mesencephalic reticular formation (MFR) in 7 Ss significantly improved the accuracy of a perceptually difficult successive discrimination between a smooth light and a rapidly flickering light. Despite similar baseline conditions, including accuracy, MRF stimulation did not affect accuracy when the flickering light was maintained at an easily detectable 5 Hz. Accuracy of the perceptually difficult discrimination was not affected by changes in water deprivation or by electrical stimulation of the inferior colliculus or the fornical area of the limbic system. These findings suggest that the stimulation-induced improvement in the accuracy of the perceptually difficult flicker discrimination was not due to nonspecific changes in motivation, arousal, or general attention or to the possible cue or alerting function of the stimulation. The failure to implicate nonsensory processes and the finding that accuracy was improved only when the light was flickering rapidly indicate that MRF stimulation increased accuracy by improving the discriminability of the rapidly flickering light. (17 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prolonged and extensive IgG immunoreactivity after severe fluid-percussion injury in rat brain

The relationships between protein extravasation, morphological changes in neurons, and reactive changes in axons were evaluated in rats subjected to right lateral fluid-percussion injury to the brain (4.8-5.6 atm, 20 ms). Serial sections of the brain were immunostained with antibodies to rat immunoglobulin G (IgG) and 68-kDa neurofilament at 1 h to 2 weeks after injury or sham injury. Ischemic changes in neurons were noted in the injured cortex at 6-48 h after injury, and macroscopic hemorrhages were noted in the right corpus callosum and external capsule at 1 h to 1 week after injury. Extracellular IgG immunostaining was observed in the right cortex and right hippocampus at 1 h to 1 week after injury, and in the cortices and hippocampi bilaterally at 2 weeks after injury, but was most prominent in those regions at 24 h after injury. Intracellular IgG staining was noted in the neurons of cortices, hippocampi, brainstem, and cerebellum at 1 h to 2 weeks after injury. The number of IgG immunoreactive neurons was greatest at 1 week after injury. Thickened IgG immunoreactive axons and reactive axonal changes seen with neurofilament immunostaining were both in the similar region of the brainstem at 1 h to 1 week after injury. It appears that prolonged and widespread breakdown of the blood-brain barrier to plasma protein occurs after severe concussive brain injury and that this breakdown is not always accompanied by morphological changes. Intra-axonal IgG immunostaining provides additional clues to the pathogenesis of axonal damage following diffuse brain injury.     

Complement-fixing elicited antibodies are a major component in the pathogenesis of xenograft rejection

Hamster to rat cardiac xenografts undergo delayed rejection as compared with the hyperacute rejection of discordant xenografts. Elicited xenoreactive Abs (EXA) are thought to initiate hamster to rat cardiac xenograft rejection. In this study, we demonstrate that following transplantation of a hamster heart, rats generated high levels of EXA. Adoptive transfer into naive recipients of purified IgM, IgG2b, or IgG2c, but not IgG1 or IgG2a EXA, induced xenograft rejection in a complement-dependent manner. Ability of EXA to cause rejection correlated with complement activation, platelet aggregation, and P-selectin expression in the xenograft endothelium. Cyclosporin A (CyA) administration, after transplantation, totally suppressed IgG1, IgG2a, IgG2b, and IgG2c EXA, and inhibited IgM EXA production, but failed to overcome rejection. Administration of cobra venom factor (CVF), 1 day before and at the time of transplantation, resulted in complement inhibition during 3 days after transplantation, which failed to overcome rejection. Combination of CyA and CVF, which we have previously shown to overcome rejection, resulted in suppression of IgG EXA production and in the return of IgM XNA to preimmunization serum levels, 3 to 7 days after xenotransplantation, while complement remained inhibited. Thus, under CyA/CVF treatment, complement activation by hamster cells was suppressed following xenotransplantation, and presumably for this reason xenograft rejection did not occur. In conclusion, our data demonstrate that EXA play a pivotal role in the pathogenesis of xenograft rejection and that CyA and CVF suppress xenograft rejection by preventing exposure of xenograft endothelial cells to complement activation by EXA.     

Habituation of the acoustic startle response in rats after lesions in the mesencephalic reticular formation or in the inferior colliculus.

Extensive damage to the mesencephalic reticular formation (MRF) in 24 male albino rats altered long-term habituation of the acoustic startle response without disrupting short-term habituation. The MRF lesions did not alter initial startle amplitudes, but the Ss with lesions were unable to attain as low a long-term asymptote of habituation as could 21 control Ss. Subsequent manipulation of stimulus intensity and interstimulus interval revealed no differences in short-term habituation between the 2 groups. Large lesions to the inferior colliculus (IC) of 22 Ss did not disrupt long-term habituation of the acoustic startle response, but these Ss were unable to suppress responding as much as controls to intense stimuli presented rapidly. The deficits in long-term habituation following MRF lesions suggest a disruption of an extrinsic, inhibitory mechanism of habituation. The deficits following IC lesions could have been due either to a disruption of a short-term habituation mechanism or to an increase in response sensitization produced by the lesions. (30 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mesencephalic reticular formation lesions made after habituation training abolish long-term habituation of the acoustic startle response in rats.

Lesions to the mesencephalic reticular formation (MRF) in rats severely attenuate the acquisition of long-term habituation of the startle response when the lesions are made prior to habituation training. The present experiments extend the finding of habituation deficits to animals with MRF damage made after the animals have habituated to an auditory stimulus. Following habitation training, some animals received lesions to the MRF. The startle amplitudes of these animals immediately changed from control levels to levels indistinguishable from those of animals that never habituated across days—animals with MRF lesions made prior to habituation training. The mechanism responsible for long-term habituation appears to be a progressive increase in activity within a long-term habituation pathway extrinsic to the reflex circuit for the startle response, but the synaptic mechanisms responsible for this change are unknown. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The reticular zone of the rat adrenal gland 60 days after exposure to a chemical fertilizer

The author examined the adrenal glands of rats that were kept in a workshop of an NPK fertilizer factory for 30 days and then for 60 days in the laboratory. Histochemical examination of the reticular zone revealed an increase in neutral lipids and triglycerides and a decrease in phospholipids. The nucleic acid content, predominantly RNA, was enhanced. Although the acid phosphatase activity was slightly lowered, both succinate dehydrogenase and monoamine oxidase activities were increased. The results indicate that exposure of rats to NPK fertilizer had a stimulating effect on the reticular zone of their adrenal glands.