Modulatory effects of serotonin on excitatory amino acid responses and sensory synaptic transmission in the ventrobasal thalamus

Excitatory amino acid receptors are thought to mediate sensory input to the ventrobasal thalamus. There is evidence for a brainstem serotonergic projection to the ventrobasal thalamus which may have a modulatory role. The possibility that serotonin may selectively modulate responses to excitatory amino acid receptor agonists, and its effects on sensory synaptic transmission has been examined in the rat ventrobasal thalamus in vivo. Iontophoretic ejection of serotonin at low currents produced a marked facilitation of responses to excitatory amino acids. In contrast, excitatory responses to cholinomimetic agonists were attenuated. Synaptic transmission was concomitantly enhanced or unchanged in these circumstances. Higher serotonin ejection currents reversed the facilitation, or inhibited excitatory amino acid responses and synaptic transmission. It is concluded that serotonin can modulate responses to excitatory amino acids relatively selectively and that synaptic transmission of somatosensory information through the ventrobasal thalamus may be susceptible to brainstem serotonergic modulation.     

Distribution of putative amino acid transmitters, choline acetyltransferase and glutamate decarboxylase in the inferior colliculus.

Levels of glutamic acid, aspartic acid, glycine, taurine, alanine, choline acetyltransferase, and glutamate decarboxylase were measured in ten regions of the inferior colliculus in the cat. None of these substances were uniformity distributed in the colliculus. The highest concentrations of asparate occurred in central regions, whereas those of glycine were in ventral central regions. The distributions of glutamic acid and glutamate decarboxylase were highly correlated, with both being generally high in dorsal regions. There was also a high correlation in the distributions of taurine and alanine, with these substances having their highest concentrations in the posterior region and lowest concentrations in the anterior region. The concentration of choline acetyltransferase was highest in the anterior region. No consistent changes in any of the substances were seen following elimination of inputs ascending to the colliculus via the dorsal and intermediate acoustic striae. Small decreases in glutamic acid were seen in two extracentral regions following removal of the auditory cortex.The nonuniform distribution of the substances that were analyzed suggest that there may be previously undescribed differences in the structure and function of the inferior colliculus. The lack of change in the content of choline acetyltransferase and glutamate decarboxylase after lesion of inputs from the cortex or cochlear nucleus makes it unlikely that acetylcholine or α-aminobutyrate are transmitters in these pathways.     

Synapse- and subtype-specific modulation of synaptic transmission by nicotinic acetylcholine receptors in the ventrobasal thalamus

The rodent thalamic ventrobasal complex (VB) which is a subdivision of somatosensory thalamus receives two excitatory inputs through the medial lemniscal synapse, which is a sensory afferent synapse, and the corticothalamic synapse from layer VI of the somatosensory cortex. In addition, the VB also receives cholinergic inputs from the brain stem, and nicotinic acetylcholine receptors (nAChRs) are highly expressed in the VB. Little is known, however, how acetylcholine (ACh) modulates synaptic transmission at the medial lemniscal and corticothalamic synapses in the VB. Furthermore, it remains unclear which subtype of nAChRs contributes to VB synaptic transmission. We report here that the activation of nAChRs presynaptically depressed corticothalamic synaptic transmission, whereas it did not affect medial lemniscal synaptic transmission in juvenile mice. This presynaptic modulation was mediated by the activation of nAChRs that contained α4 and β2 subunit, but not by α7 nAChRs. Moreover, galanthamine, an allosteric modulator of α4β2α5 nAChR, enhanced the ACh-induced depression of corticothalamic excitatory postsynaptic currents (EPSCs), indicating that α4β2α5 nAChRs at corticothalamic axon terminals specifically contribute to the depression of corticothalamic synaptic transmission.     

Development of substance P, Leu-enkephalin and serotonin profiles in the lateral geniculate nuclear complex of albino rat

Immunohistochemical studies for analysing the development of the profile of two peptides — substance P (SP) and Leu-enkephalin (Leu-ENK), and serotonin (SER) — have been conducted on the lateral geniculate nuclear (LGN) complex of albino rats at gestation day 18 and various postnatal age periods. SP immunoreactivity is found to increase from 1 day postnatal (DPN) up to 20 DPN and decrease thereafter, whereas the SER and Leu-ENK-immunoreactive fibres and terminals seen as occasional fibres at 1, 5, and 10 DPN are better visualized from 20 DPN and gradually increase up to 40 DPN. The possible role and significance of the changes seen in these putative neurotransmitters/neuromodulators with development are discussed.     

Co-expression of neuropeptides in the cat's striatum: an immunohistochemical study of substance P, dynorphin B and enkephalin.

The expression of tachykinin-like and opioid-like peptides was studied in medium-sized neurons of the caudate nucleus in tissue from adult cats pretreated with colchicine. Two methods, a serial thin-section peroxidase-antiperoxidase technique and a two-fluorochrome single-section technique, were applied. Quantitative estimates were made mainly with the peroxidase-antiperoxidase method. The numbers of neurons expressing substance P-like, dynorphin B-like, and enkephalin-like immunoreactivity were recorded in regions identified, respectively, as striosomes and extrastriosomal matrix. Striosomes were defined by the presence of clustered substance P-positive and dynorphin B-positive neurons and neuropil. Tests for the co-existence of enkephalin-like peptide and glutamate decarboxylase-like immunoreactivity were also made with the peroxidase-antiperoxidase method. Co-expression of substance P-like and dynorphin B-like immunoreactivities was the rule both in striosomes and in the matrix. In striosomes, substance P-like immunoreactivity was found in 96% of dynorphin B-immunoreactive neurons, and in the matrix 89% of dynorphin B-positive cells contained substance P-like immunoreactivity. Substance P/dynorphin B-positive neurons corresponded to over half (57%) of the neurons in striosomes but only 39% of the neurons in the matrix. Both in the matrix and in striosomes, about two-thirds of all neurons (63% and 65%, respectively) were identified as enkephalin-positive. Among all substance P/dynorphin B-positive medium-sized neurons, 76% also contained enkephalin-like antigen. The enkephalin-positive neurons characterized by triple peptide co-existence (enkephalin/substance P/dynorphin B) represented a mean of 63% of striosomal enkephalin-positive neurons (41% of all striosomal neurons) and 35% of matrical enkephalin-positive neurons (26% of all matrical neurons). Finally, nearly all enkephalin-positive neurons were immunoreactive for glutamate decarboxylase, and therefore probably GABAergic, but only about half the glutamate decarboxylase-positive population was enkephalin-immunoreactive. These findings suggest that neuropeptides from three distinct precursors may be co-localized in single medium-sized neurons in the striatum, and that the differential patterns of co-expression of substance P-like, dynorphin B-like, and enkephalin-like peptides may confer functional specializations upon subpopulations of GABAergic neurons giving rise to the efferent projections of the striatum. The linked expression of substance P-like and dynorphin B-like peptides in single neurons both in striosomes and matrix suggests that some regulatory mechanisms controlling peptide expression apply regardless of compartment.(ABSTRACT TRUNCATED AT 400 WORDS)     

Actions of excitatory amino acid antagonists on synaptic potentials of layer II/III neurons of the cat's visual cortex

Summary Actions of excitatory amino acid (EAA) antagonists on the responses of cells in layers II/III and IV of the cat's visual cortex to stimulation of layer VI and the underlying white matter were studied in slice preparations. Antagonists used were 2-amino-5-phosphonovalerate (APV), a selective antagonist for the N-methyl-D-aspartate (NMDA) type of EAA receptors, and kynurenate, a broadspectrum antagonist for the three types of EAA receptors. In extracellular recordings it was demonstrated that most of the layer II/III cells were sensitive to APV, while the great majority of the layer IV cells were not, By contrast, kynurenate suppressed the responses completely in both layers. Excitatory post-synaptic potentials (EPSPs) evoked by stimulation of layer VI and the while matter were recorded intracellularly from layer II/III neurons. To determine whether the EPSPs were elicited mono- or polysynaptically, the synaptic delay for each EPSP was calculated from a pair of onset latencies of EPSPs evoked by stimulation of the two sites. Forty-two percent of the layer II/III cells were classified as having monosynaptic EPSPs. In 60% of these monosynaptic cells, the rising slope of the EPSPs was reduced by APV while in the other 40%, it was not. In the former (APV-sensitive cells), subtraction of the APV-sensitive component from the total EPSP indicated that the onset latency of the NMDA receptor-mediated component was roughly equal to that of the non-NMDA component. In the latter (APV-resistant cells), only the slowly-decaying component was in part mediated by NMDA receptors. The conduction velocities of the afferent fibers innervating APV-resistant cells were slower than those of the APV-sensitive cells, suggesting that both types of cells are innervated by different types of afferents. The polysynaptic EPSPs of almost all layer II/III cells were sensitive to APV. The subtraction method indicated that the NMDA component had about the same magnitude as the non-NMDA components. When the slices were superfused by a Mg²⁺-free solution, the EPSPs were potentiated dramatically, but this potentiation was reduced to the control level during the administration of APV. Similarly, APV-sensitive components were potentiated during the administration of bicuculline, a selective antagonist for gamma-aminobutyric acid receptors of A type. These results suggest that NMDA receptors participate, at varying degrees, in excitatory synaptic transmission at most layer II/III cells in the cat's visual cortex, and their actions appear to be regulated by intracortical inhibition.     

Role of substance P amino terminal metabolites in substance P-induced desensitization in mice.

Intrathecal injection of mice with substance P or its C-terminal fragments evokes a well documented behavioral syndrome characterized by caudally-directed biting and scratching. We have previously shown that repeated injections of substance P result in naloxone-sensitive desensitization to this substance P-induced behavior, possibly through interactions of N-terminal fragments of substance P with mu opiate binding sites. The present investigation tests the hypothesis that substance P metabolites play a role in the development of desensitization to substance P by using the biting and scratching behavioral paradigm. While substance P-induced behaviors are produced by as little as 1 pmol of substance P, repeated injections of 7.5 pmol at 60-s intervals was found to be the minimum dose capable of causing desensitization. The C-terminal peptides, substance P3-11 and substance P5-11, elicited substance P-like behaviors, but repeated injection of these compounds did not result in desensitization to this behavior. In contrast to C-terminal fragments, intrathecal injection of N-terminal fragments, (substance P1-4, substance P1-7 and substance P1-9), did not elicit any overt substance P-like behaviors when administered alone, but when co-administered with substance P, decreased the magnitude of substance P-induced behaviors in a dose-related fashion. Various peptidase inhibitors significantly inhibited the catabolism of co-administered substance P. Co-administration of substance P with peptidase inhibitors enhanced and prolonged the substance P-induced behavioral episode, but also prevented the development of substance P-induced desensitization. Together these results support the hypothesis that the accumulation of endogenously generated N-terminal metabolites of substance P mediate desensitization to substance P-induced behaviors in the spinal cord. Substance P metabolism may therefore decrease ongoing substance P activity both by the hydrolysis of the C-terminal portion of substance P as well as by the production of N-terminal metabolites that are capable of inhibiting the effects of substance P.     

犬脑干缺血后递质性氨基酸含量变化的实验研究

目的和方法：观察犬脑干缺血不同时点递质性氨基酸含量的变化及其与神经元损伤的关系，以探讨递质性氨基酸在脑干缺血损伤中的可能作用。结果：犬脑干缺血３０ｍｉｎ，兴奋性氨基酸（ＥＡＡｓ）递质含量升高不明显，神经元呈轻度缺血损伤；缺血３ｈ后，ＥＡＡｓ含量显著升高，并随着缺血时间的延长不断增加，神经元亦从中度发展至重度缺血损伤。抑制性氨基酸（ＩＡＡｓ）递质在缺血３ｈ后开始有显著升高；至缺血１２ｈ，两者不再增高。即使在缺血后期，ＩＡＡｓ有明显增高，神经元损伤仍无减轻迹象。结论：ＥＡＡｓ参与了脑干缺血损伤病理过程；脑干缺血后期增高的ＩＡＡｓ对缺血损伤的神经保护作用表现不明显     

Excitatory amino acid transmitters in neuronal circuits of the cat visual cortex

To test a possibility that glutamate (Glu) and aspartate (Asp) are transmitters in the visual cortex and to locate their operating sites in the cortical circuitry, we studied effects of microiontophoretic application of Glu/Asp antagonists on visual responses of cortical neurons in the cat. The antagonists tested were kynurenic acid (KYNA), cis-2,3-piperidine dicarboxylic acid, and gamma-D-glutamylglycine. Among these antagonists, KYNA was most effective in blocking visual responses of cortical neurons; it eliminated visual responses in 156 of the 188 cells tested. Usually the maximal suppressive effect appeared 20-30 s after starting KYNA application and recovery of cell's responsiveness 30-60 s after stopping the application. KYNA antagonized excitations induced by ionophoretic application of Glu and Asp but did not block those by acetylcholine, suggesting that KYNA is a selective antagonist of Glu/Asp, and its action is not due to general depressant effects. This suggestion was further supported by the observation that in corticogeniculate cells the latency and probability of invasion of antidromic spikes into the somatodendritic part following electrical stimulation of the lateral geniculate were not changed while visual responses were completely suppressed by KYNA. In terms of actions of the three agonists which give the basis for classifying excitatory amino acid receptors into at least three types, KYNA antagonized excitations by N-methyl-D-aspartic acid (NMDA) and kainate in almost all the cells tested but did not block those by quisqualate in about half of the cells. These results suggest that KYNA reacts more preferentially with NMDA and kainate receptors than with quisqualate receptors. Effectiveness of KYNA was related to types of receptive fields of cells and to their laminar locations. In 79 of the 104 simple cells tested, KYNA completely suppressed their visual responses, while such a complete block was seen in only 18 of the 68 complex and 3 of the 16 special complex cells. The great majority of the cells in layers IVab, IVc and the upper part of layer VI were completely suppressed by KYNA, whereas most of the cells in the other layers were incompletely suppressed or not suppressed at all.(ABSTRACT TRUNCATED AT 400 WORDS)     

Response properties of periodontal mechanosensitive units in the cat's thalamus

Summary 1) The response characteristics of periodontal mechanosensitive neurons in the thalamic nucleus were studied by using 15 adult cats anesthetized with alphachloralose (40 mg/kg, i.v.). 2) 468 periodontal mechanosensitive units (PM units) responsive to light mechanical stimulation of the teeth were recorded from a medioventral aspect of the nucleus ventralis posteromedialis (VPM). Of these neurons, 213 units (45.5%) were slowly adapting, and 255 units (54.5%) were rapidly adapting. 3) The receptive field of the PM units was represented by the number of receptive quadrants on the dental arches of both jaws. About half of the PM units (279, 59.6%) were one-quadrant units. Of these neurons, 69 (14.7%) were single tooth units. Two-quadrant, three-quadrant and four-quadrant units numbered 123 (26.3%), 3 (0.6%) and 63 (13.5%) respectively. Of the PM units detected, 246 units (52.6%), 124 units (26.4%) and 98 units (20.9%) responded to mechanical stimulation of the teeth on only the contralateral side, on only the ipsilateral side and on both sides, respectively. 4) One-quadrant units were distributed mainly in the rostral part of the PM area, and four-quadrant units were found in the caudal part of the PM area. A somatotopic organization for each tooth was not found. 5) The incidence of single tooth units in the thalamus was extremely low, compared with those in the primary afferents and in the trigeminal nuclear complex. Most of the thalamic neurons had larger receptive fields than both the primary afferents and the trigeminal nuclear complex neurons. 6) The high incidence of fourquadrant units at the caudal part of the PM area suggests that many PM fibers converge there. However, it is still unclear whether these fibers come through the intrathalamic neurons or directly from the trigeminal nuclear complex.     

Action of amino acid transmitters on glial cells in tissue culture

Intracellular recordings were made from glial cells of human and rat spinal cord grown in tissue culture. The membrane potentials of the glial cells were usually higher than those recorded from neurones. Addition of the putative neurotransmitters glycine, GABA, glutamate and aspartate to the bathing fluid in a concentration of 10^?4 M had no effect on the membrane potential of most glial cells tested.     

Excitatory amino acid transmitters and their receptors in neural circuits of the cerebral neocortex

In 1954, L-glutamate (Glu) and L-aspartate (Asp) were first suggested as being excitatory synaptic transmitters in the cerebral cortex. Since then, evidence has mounted steadily in favor of the view that Glu and Asp are major excitatory transmitters in the neocortex. Many of the experimental studies which reported how Glu/Asp came to satisfy the criteria for transmitters in the neocortex are reviewed here, according to the methods employed. Since the question of which particular synaptic sites in cortical neural circuits Glu/Asp operate as excitatory transmitters has not previously been reviewed, particular attention is given to efferent, afferent and intrinsic neural circuits of the visual and somatosensory cortices, where circuitry is relatively clearly delineated. Recent studies using chemical assays of released amino acids, high-affinity uptake mechanisms of Glu/Asp from nerve terminals, the direct micro-iontophoretic administration of Glu/Asp antagonists, and immunocytochemical techniques have demonstrated that almost all corticofugal efferent projections employ Glu/Asp as excitatory synaptic transmitters. Evidence indicating that thalamocortical afferent projections, including geniculocortical projections and some intrinsic connections are glutamatergic, is also reviewed. Thus, the results highlighted here indicate that the main framework of neocortical circuitry is operated by Glu/Asp. Pharmacological studies indicate that synaptic receptors for Glu/Asp can be classified into a few subtypes, including N-methyl-D-aspartate (NMDA) and quisqualate/kainate (non-NMDA) types. Some evidence indicating the sites of operation of NMDA and non-NMDA receptors in neocortical circuitry is reviewed, and the distinct, functional significance of these two types of Glu/Asp receptors in information processing in the neocortex is proposed.     

Possible coexistence of amino acid (γ-aminobutyric acid), amine (dopamine) and peptide (substance P); neurons containing immunoreactivities for glutamic acid decarboxylase,tyrosine hydroxylase and substance P in the hamster main olfactory bulb

Summary The coexistence of immunoreactivities for glutamic acid decarboxylase (GAD), tyrosine hydroxylase (TH) and substance P (SP) was revealed in the hamster main olfactory bulb, using the peroxidase-antiperoxidase immunohistochemical method. Adjacent 40 m thick Vibratome sections were incubated in different antisera and those cells which were bisected by the plane of sectioning were identified at the paired surfaces of two consecutive sections. The coexistence of the immunoreactivities for 1) TH and GAD, 2) TH and SP and 3) GAD and SP in the same cells could thus be determined by observing the immunoreactivity of the two halves of the cell incubated in two different antisera. About 70% of TH-like immunoreactive (TH-LI) neurons in the periglomerular region also contained GAD-like immunoreactivity, whereas about 45% of GAD-LI ones were also TH-like immunoreactive. Furthermore, almost all (more than 95%) of SP-LI neurons contained both GAD-like and TH-like immunoreactivities. These observations indicate that in the periglomerular region of the hamster main olfactory bulb, some neurons (about 9% of all neurons containing TH-like and/or GAD-like immunoreactivities) may contain three different categories of neuroactive substances, that is, amino acid (GABA), amine (dopamine) and peptide (SP).     

Dilatory responses to acetylcholine, calcitonin gene-related peptide and substance P in the congestive heart failure rat

It was examined to what extent congestive heart failure (CHF) in rats, induced by ligation of the left coronary artery, affects the vascular responses to the vasodilatory substances acetylcholine (ACh), calcitonin gene-related peptide (CGRP), and substance P (SP). After induction of CHF status, the basilar, mesenteric and renal arteries and the iliac vein were studied in vitro. Dilatory responses were determined in relation to pre-contraction by the thromboxane mimetic U46619. Sham-operated animals (Sham) served as controls. U46619 induced stronger contraction in CHF basilar and renal arteries compared with the corresponding segments in Sham. ACh induced concentration-dependent dilations in all vessels examined with no difference of maximum relaxation or potency between CHF and Sham. SP induced weak dilations in all arteries examined while the response was markedly attenuated in CHF iliac veins compared with Sham (Emax% 12.2 +/- 3.4 vs. 32.3 +/- 4.8, P = 0.01). The CGRP induced dilation in the CHF basilar artery was weaker (Emax% 18.6 +/- 6.5 vs. 66.9 +/- 5.0, P < 0.001) and less potent (pEC50: 8.2 +/- 0.2 vs. 9.0 +/- 0.2, P = 0.01) compared with Sham. Further, CGRP was less potent in the renal artery of CHF rats compared with Sham (pEC50: 8.1 +/- 0.2 vs. 9.5 +/- 0.3, P < 0.01). In the CHF iliac vein, CGRP was more potent compared with Sham (pEC50: 9.7 +/- 0.4 vs. 8.3 +/- 0.4, P < 0.05). It can be concluded CHF is accompanied by alterations in the vascular response to the dilatory substances studied. The changes differ between vascular beds and between the different substances.     

The relationship of calbindin-containing neurons with substance P, Leu-enkephalin and cholecystokinin fibres: An immunohistochemical study in the rat thalamus

In the rat thalamus, immunoreactivity for the calcium binding protein calbindin (Cb) is mostly confined to neuronal cell bodies, sometimes revealing proximal dendrites, of the midline, intralaminar and posterior regions. Substance P (SP)-, cholecystokinin (CCK)- and Leu-enkephalin (L-ENK)-immunoreactive (ir) elements in the thalamus are fibre-like structures, intermingled with punctate elements probably representing axonal arborizations and their synaptic boutons. These peptidergic fibres are unevenly distributed in several thalamic domains, including the areas that contain Cb-ir neurons. The relationship between Cb-ir cell bodies and these three different peptidergic systems of thalamic innervation was studied with immunohistochemistry. Single-labelling experiments on adjacent sections and double immunostaining on the same section were performed. A considerable overlap between Cb-ir perikarya and SP-ir fibres was found in most thalamic nuclei. In particular, in the intralaminar nuclei and posterior complex. SP-ir punctate elements were frequently observed in close proximity to Cb-ir cell bodies and dendrites. On the other hand, no consistent topographical correspondence between Cb-ir perikarya and CCK- or L-ENK-ir fibres was evident. Altogether, the present data suggest a selective anatomical and, possibly, functional relationship between SP and Cb in at least a subpopulation of rat thalamic neurons.     

Excitatory amino acid antagonists inhibit synaptic responses in the guinea pig hypothalamic paraventricular nucleus.

1. The effects of specific excitatory amino acid (EAA) antagonists on evoked excitatory synaptic responses were studied in the hypothalamic paraventricular nucleus (PVN) of the guinea pig, by the use of the in vitro slice preparation. Intracellular recordings were obtained from paraventricular neurons, and excitatory postsynaptic potentials (EPSPs) and currents (EPSCs) were induced by perifornical electrical stimulation. To reduce the influence of a potential gamma-aminobutyric acidA (GABAA) inhibitory component on the synaptic responses, all experiments were performed in the presence of 50 microM picrotoxin. 2. Of 20 cells tested, 13 had electrophysiological characteristics similar to magnocellular neuropeptidergic cells (MNCs) and 7 displayed low-threshold Ca2+ spikes (LTSs). No difference was detected in the effect of the antagonists on the synaptic responses of cells with or without LTS potentials. 3. The broad-spectrum EAA antagonist kynurenic acid decreased the amplitude of the EPSPs and EPSCs in a dose-dependent manner: the mean decrease was 5% for 100 microM, 43% for 300 microM, and 70% for 1 mM. 4. The quisqualate/kainate-receptor-selective antagonist 6-cyano-2,3-dihydroxy-7-nitroquinoxaline (CNQX) induced a dose-dependent decrease of the EPSPs and EPSCs: 1 microM had no detectable effect, 3 and 10 microM caused 30 and 70% decreases, respectively, and 30 microM blocked the response almost completely. This effect was not accompanied by a change in resting membrane potential or input resistance and was slowly reversible. 5. The N-methyl-D-aspartate (NMDA)-receptor-selective antagonist DL-2-amino-5-phosphonopentanoic acid (AP5), applied at 30 and 300 microM, reduced slightly the amplitude of the decay phase of the EPSP but did not significantly affect the peak amplitude. In some cells, the current-voltage relationship of the decay phase of the EPSC revealed a region of negative slope conductance between -70 and -40 mV. 6. These results suggest that 1) glutamate or a related EAA is responsible for the fast excitatory input to magnocellular and parvocellular neurons in the PVN and probably also for cells around PVN, 2) a quisqualate/kainate receptor type is responsible for the rising phase and peak amplitude of the synaptic current, and 3) an NMDA receptor contributes to the late part of the synaptic response.     

The activity of olfactory receptor cells is affected by acetylcholine and substance P

The effects of acetylcholine (ACh) and substance P (SP) on the unit activity of receptor cells recorded from the superfused frog olfactory mucosa were studied. Single neurones were excited or, more rarely, depressed by the application of chemicals. Cholinergic antagonists were used to investigate the involvement of nicotinic and muscarinic receptors in the recorded responses. The ACh-evoked firing was antagonized by D-tubocurarine (D-TC), atropine (ATR) and SP. Responses to SP appeared to be D-TC resistant, but activation by the peptide was moderately antagonized by ATR. The results suggest that ACh and SP could affect the functioning of the olfactory receptor cells.     

Kainic acid induced seizures: changes in somatostatin, substance P and neurotensin

The neuropeptides somatostatin, neurotensin and substance P were investigated in rats during and after limbic seizures induced by systemic injection of kainic acid (10 mg/kg, i.p.). Three hours after injection of the toxin, pronounced decreases (40-50%) in somatostatin-like immunoreactivity in frontal cortex, striatum, dorsal hippocampus and amygdala/pyriform cortex were observed. Concomitantly, neurotensin-like and substance P-like immunoreactivities were also reduced in the frontal cortex and the hippocampus. These early decreases in peptide levels may result from increased release and subsequent inactivation of the peptides during acute seizures. At later time intervals, 3, 10 and 30 days after injection of kainic acid, the initially decreased peptide levels were partially normalized. However, the reduction in somatostatin-like immunoreactivity in amygdala/pyriform cortex and striatum persisted up to 30 days. Neurotensin-like immunoreactivity remained decreased in the frontal cortex. On the other hand, neurotensin- and substance P-like immunoreactivities were increased in the striatum and substantia nigra 10-30 days after injection of kainic acid. These late changes in peptide levels may suggest destruction of peptidergic neurons or adaptive changes induced by the convulsions. Pretreatment of rats with cysteamine (100 mg/kg, i.p.), an agent which decreases brain somatostatin levels, had no effect on the intensity of kainic acid induced convulsions, although a slightly earlier onset of seizures was observed. The changes in peptide levels, especially the marked decreases in somatostatin content after systemic injection of kainic acid, suggest considerable acute and chronic alterations in peptidergic systems caused by limbic convulsions.     

Experimental peripheral neuropathy decreases the dose of substance P required to increase excitatory amino acid release in the CSF of the rat spinal cord.

Partial ligation of the sciatic nerve of rats produces hyperalgesia similar to that seen in humans following nerve injury. In this study, we used microdialysis of the spinal cord cerebral spinal fluid (CSF) to test the hypothesis that hyperalgesia is due to an enhanced release of excitatory amino acids (EAA) in response to substance P (SP). Intrathecal SP caused release of aspartate and glutamate in the CSF of rats with partial sciatic ligation at a dose of SP that did not cause release in sham operated animals. Neonatal capsaicin pretreatment blocked SP-induced EAA release in both sham and sciatic ligated animals. Release of EAAs in ligated animals was not significantly different from release in sham-operated animals following higher doses of SP or chemical nociceptive stimulation. These results demonstrate a partial sciatic ligation-induced decrease in the dose of SP required to initiate EAA release in the CSF of the spinal cord, a change which could play an important role in hyperalgesia.