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1.
gamma-Aminobutyric acid (GABA)-stimulated release of L-glutamate from various neuronal regions of acute mouse hippocampal slices was detected with a patch sensor that responds to L-glutamate at the sub-micromolar level. The response of the patch sensor to L-glutamate was evaluated in terms of an integrated current. The integrated current increased with the concentration of L-glutamate ranging from 0.50 to 5.0 microM. By using the patch sensor, GABA-induced L-glutamate release from acute mouse hippocampal slices was detected. The effect of antagonists for GABA(A) and GABA(B) receptors on the L-glutamate release was also investigated. The GABA (25 microM) stimulation induced the release of L-glutamate via GABA(A) receptor in the CA1 region, but GABA did not induce L-glutamate release in the CA3 region. However, in the presence of the GABA(B) receptor antagonist (3-aminopropyl)(diethoxymethyl)phosphinic acid (CGP-35348), release of L-glutamate in the CA3 region was evoked by GABA stimulation. The glutamate release was completely suppressed when both GABA(A) and GABA(B) receptor were inhibited. The current results show that the glutamate release in the CA3 region occurs via a GABA(A) pathway when GABA(B) receptors are inhibited.  相似文献   

2.
In this study, we examined effects of chemical stimulation of the ventrolateral region of the midbrain periaqueductal gray (vl PAG) on airway smooth muscle tone. We observed that in anesthetized, paralyzed, and artificially ventilated ferrets, vl PAG stimulation elicited airway smooth muscle relaxation. To clarify the mechanisms underlying this observation, we examined the GABA-GABA(A) receptor signaling pathway by 1) examining the expression of GABA(A) receptors on airway-related vagal preganglionic neurons (AVPNs) located in the rostral nucleus ambiguus region (rNA), by use of receptor immunochemistry and confocal microscopy; 2) measuring GABA release within the rNA by using microdialysis; and 3) performing physiological experiments to determine the effects of selective blockade of GABA(A) receptors expressed by AVPNs in the rNA region on vl PAG-induced airway relaxation, thereby defining the role of the GABA(A) receptor subtype in this process. We observed that AVPNs located in the rNA region do express the GABA(A) receptor beta-subtype. In addition, we demonstrated that activation of vl PAG induced GABA release within the rNA region, and this release was associated with airway smooth muscle relaxation. Blockade of the GABA(A) receptor subtype expressed by AVPNs in the rNA by bicuculline diminished the inhibitory effects of vl PAG stimulation on airway smooth muscle tone. These data indicate, for the first time, that activation of vl PAG dilates the airways by a release of GABA and activation of GABA(A) receptors expressed by AVPNs.  相似文献   

3.
Previous findings have shown that some of the neurons in the median preoptic nucleus (MnPO) receive both catecholaminergic inputs from the brainstem and angiotensinergic inputs from the subfornical organ (SFO), and that alterations in the function of the brain renin-ANG system are implicated in hypertension, especially in spontaneous hypertensive rats (SHR). In an attempt to clarify the action of these inputs on MnPO neurons and to find the difference in the action between normotensive Wistar-Kyoto (WKY) rats and SHR, we used microdialysis to investigate the effects of injections of saralasin (Sar), an angiotensin II (ANG II) antagonist, into the third ventricle (3V) on monoamine release in the MnPO area of awake WKY and SHR. The content of noradrenaline (NA) in the MnPO area was significantly higher in SHR. No significant differences were observed between WKY and SHR in the concentrations of dopamine (DA) and of its two metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). In both WKY and SHR, Sar (Sar, 5 microg in 1 microl, three injections at 2-h intervals) injected into the 3V significantly decreased the extracellular concentrations of NA, DOPAC and HVA in the MnPO area. The decreases were much greater in SHR than in WKY rats. Similar injections of saline vehicle had no significant effect on the extracellular levels of NA, DA and the metabolites. These results suggest that central angiotensinergic circuits may serve to increase NA and DA release in the MnPO area, and support that a disorder in the ANG system may contribute, in part, to the elevated blood pressure of SHR.  相似文献   

4.
In order to assess a role of 5-HT(1B) receptors for regulation of GABA transmission in the ventral tegmental area (VTA), VTA slices from the rat were incubated with [(3)H]GABA and beta-alanine, and superfused in the presence of nipecotic acid and aminooxyacetic acid. [(3)H]GABA release was induced by exposures to the medium containing 30 mM potassium for 2 min. The results showed that high potassium-evoked [(3)H]GABA release was sensitive to calcium withdrawal or blockade of sodium channels by tetrodotoxin, suggesting that tritium overflow induced by high potassium derived largely from neuronal stores. Administration of CP 93129 (0.15 and 0.45 microM), a 5-HT(1B) receptor agonist, or RU 24969 (0.15 and 0.45 microM), a 5-HT(1B/1A) receptor agonist, but not 8-OH-DPAT (0.45 microM), a 5-HT(1A) receptor agonist, inhibited high potassium-evoked [(3)H]GABA release in a concentration-related manner. The RU 24969-induced inhibition of [(3)H]GABA release was antagonized by either SB 216641, a 5-H(1B) receptor antagonist, or cyanopindolol, a 5-HT(1B/1A) receptor antagonist, but not by WAY 100635, a 5-HT(1A) receptor antagonist. Pre-treatment with SB 216641 also antagonized CP 93129-induced inhibition of [(3)H]GABA release. The results support the hypothesis that 5-HT(1B) receptors within the VTA can function as heteroreceptors to inhibit GABA release.  相似文献   

5.
The existence of endothelin binding sites on the catecholaminergic neurons of the hypothalamus suggests that endothelins (ETs) participate in the regulation of noradrenergic transmission modulating various hypothalamic-controlled processes such as blood pressure, cardiovascular activity, etc. The effects of ET-1 and ET-3 on the neuronal release of norepinephrine (NE) as well as the receptors and intracellular pathway involved were studied in the rat anterior hypothalamus. ET-1 (10 nM) and ET-3 (10 nM) diminished neuronal NE release and the effect blocked by the selective ET type B receptor antagonist BQ-788 (100 nM). N(omega)-nitro-L-arginine methyl ester (10 microM), methylene blue (10 microM), and KT5823 (2 microM), inhibitors of nitric oxide synthase activity, guanylate cyclase, and protein kinase G, respectively, prevented the inhibitory effects of both ETs on neuronal NE release. In addition, both ETs increased nitric oxide synthase activity. Furthermore, 100 microM picrotoxin, a GABA(A)-receptor antagonist, inhibited ET-1 and ET-3 response. Our results show that ET-1 as well as ET-3 has an inhibitory neuromodulatory effect on NE release in the anterior hypothalamus mediated by the ET type B receptor and the involvement of a nitric oxide-dependent pathway and GABA(A) receptors. ET-1 and ET-3 may thus diminish available NE in the synaptic gap leading to decreased noradrenergic activity.  相似文献   

6.
The objective of the present study was to examine the effects of perfusion of dopamine (DA) D1- and D2-like receptor agonists in the nucleus accumbens (ACB) on the long-loop negative feedback regulation of mesolimbic somatodendritic DA release in the ventral tegmental area (VTA) of Wistar rats employing ipsilateral dual probe in vivo microdialysis. Perfusion of the ACB for 60 min with the D1-like receptor agonist SKF 38393 (SKF, 1-100 microM) dose-dependently reduced the extracellular levels of DA in the ACB, whereas the extracellular levels of DA in the VTA were not changed. Similarly, application of the D2-like receptor agonist quinpirole (Quin, 1-100 microM) through the microdialysis probe in the ACB reduced the extracellular levels of DA in the ACB in a concentration-dependent manner, whereas extracellular levels of DA in the VTA were not altered. Co-application of SKF (100 microM) and Quin (100 microM) produced concomitant reductions in the extracellular levels of DA in the ACB and VTA. The reduction in extracellular levels of DA in the ACB and VTA produced by co-infusion of SKF and Quin was reversed in the presence of either 100 microM SCH 23390 (D1-like antagonist) or 100 microM sulpiride (D2-like antagonist). Overall, the results suggest that (a) activation of dopamine D1- or D2-like receptors can independently regulate local terminal DA release in the ACB, whereas stimulation of both subtypes is required for activation of the negative feedback pathway to the VTA.  相似文献   

7.
The objectives of this study were to determine if the gamma-aminobutyric acid (GABA)(B) agonist, 3-aminopropyl (methyl) phosphinic acid (SKF97541), would increase luteinizing hormone (LH) secretion when infused by microdialysis into the medial basal hypothalamus (MBH) of the castrated ram, and to determine if the action of SKF97541 would be attenuated by co-infusion of the GABA(B) antagonist CGP52432. Initial experiments established that infusion of SKF alone, at concentrations as low as 5 microM, increased mean LH, LH pulse amplitude, and in some cases, pulse interval. In the last experiment, animals were treated with artificial cerebrospinal fluid (CSF) alone, SKF alone (30 microM), 3-[[(3, 4-dichlorophenol) methyl] amino] propyl] diethoxymethyl) phosphinic acid (CGP) alone (500 microM), or SKF plus CGP. SKF increased both mean LH and LH pulse amplitude as compared with CSF. CGP alone had no significant effect on LH, but it attenuated the effect of SKF on mean LH. These observations indicate that the stimulatory effects of GABA(B) agonists on LH pulse patterns are mediated through GABA(B) receptors and provide further evidence that GABA(B) receptors located in the MBH can regulate pulsatile GnRH-LH release.  相似文献   

8.
The objective of this study was to examine the role of dopamine (DA) receptors in the nucleus accumbens (ACB) in controlling feedback regulation of mesolimbic somatodendritic DA release in the ventral tegmental area (VTA) of Wistar rats using ipsilateral dual-probe in vivo microdialysis. Perfusion of the ACB for 60 min with the DA uptake inhibitor GBR-12909 (10-1,000 microM) or nomifensine (10-1,000 microM) dose-dependently increased the extracellular levels of DA in ACB and concomitantly reduced the extracellular levels of DA in the VTA. Coperfusion of 100 microM nomifensine with either 100 microM SCH-23390 (SCH), a D1 antagonist, or 100 microM sulpiride (SUL), a D2 receptor antagonist, produced either an additive (for SCH) or a synergistic (for SUL) elevation in the extracellular levels of DA in the ACB, whereas the reduction in the extracellular levels of DA in the VTA produced by nomifensine alone was completely prevented by addition of either antagonist. Application of 100 microM SCH or SUL alone through the microdialysis probe in the ACB increased the extracellular levels of DA in the ACB, whereas the extracellular levels of DA in the VTA remained unchanged. Overall, the results suggest that (a) increasing the synaptic levels of DA in the ACB activates a long-loop negative feedback pathway to the VTA involving both D1 and D2 postsynaptic receptors and (b) terminal DA release within the ACB is regulated directly by D2 autoreceptors and may be indirectly regulated by D1 receptors, possibly on interneurons and/or through postsynaptic inhibition of the negative feedback loop.  相似文献   

9.
Because GABA and its related enzymes have been determined in beta-cells of pancreas islets, effects of GABA on pancreatic exocrine secretion were investigated in the isolated, perfused rat pancreas. GABA, given intra-arterially at concentrations of 3, 10, 30, and 100 microM, did not exert any influence on spontaneous or secretin (12 pM)-induced pancreatic exocrine secretion. However, GABA further elevated CCK (10 pM)-, gastrin-releasing peptide (100 pM)-, or electrical field stimulation-induced pancreatic secretions of fluid and amylase dose dependently. The GABA (30 microM)-enhanced CCK-induced pancreatic secretions were completely blocked by bicuculline (10 microM), a GABA(A) receptor antagonist, but were not affected by saclofen (10 microM), a GABA(B) receptor antagonist. The enhancing effects of GABA (30 microM) on CCK-induced pancreatic secretions were not changed by tetrodotoxin (1 microM) but were partially reduced by cyclo-(7-aminoheptanonyl-Phe-D-Trp-Lys-Thr[BZL]) (10 nM), a somatostatin antagonist. In conclusion, GABA enhances pancreatic exocrine secretion induced by secretagogues, which predominantly induce enzyme secretion, via GABA(A) receptors in the rat pancreas. The enhancing effect of GABA is partially mediated by inhibition of islet somatostatin release.  相似文献   

10.
In the present study, the perifusions of whole pituitary glands of spermiating male common carp were performed in the presence of several GABAergic drugs. Muscimol (agonist of GABA(A) receptors) and bicuculline (the antagonist of the same type of GABA receptors) did not modify basal LH release. LH basal secretion was not modified when pituitaries were perifused with baclofen--an agonist of GABAB receptors. On the other hand, baclofen at doses of 10(-8) and 10(-4) M significantly decreased GnRH-A-induced LH release to about 86% and 88% of LH levels in control group, respectively. In our previous study we have shown that GABA decreased basal and GnRH-A-stimulated in vivo and in vitro LH release. In conclusion, it can be suggested that in the mature male carp GABA exerts an inhibitory influence on GnRH-stimulated LH release, probably through the inhibition of the GnRH action on gonadotropes. This inhibition seems to be mediated by the B type of GABA receptors.  相似文献   

11.
The present study was designed to examine whether trigeminal nociceptive inputs are involved in the modulation of parasympathetic reflex vasodilation in the jaw muscles. This was accomplished by investigating the effects of noxious stimulation to the orofacial area with capsaicin, and by microinjecting GABA(A) and GABA(B) receptor agonists or antagonists into the nucleus of the solitary tract (NTS), on masseter hemodynamics in urethane-anesthetized rats. Electrical stimulation of the central cut end of the cervical vagus nerve (cVN) in sympathectomized animals bilaterally increased blood flow in the masseter muscle (MBF). Increases in MBF evoked by cVN stimulation were markedly reduced following injection of capsaicin into the anterior tongue in the distribution of the lingual nerve or lower lip, but not when injected into the skin of the dorsum of the foot. Intravenous administration of either phentolamine or propranolol had no effect on the inhibitory effects of capsaicin injection on the increases of MBF evoked by cVN stimulation, which were largely abolished by microinjecting the GABA(B) receptor agonist baclofen into the NTS. Microinjection of the GABA(B) receptor antagonist CGP-35348 into the NTS markedly attenuated the capsaicin-induced inhibition of MBF increase evoked by cVN stimulation, while microinjection of the GABA(A) receptor antagonist bicuculline did not. Our results indicate that trigeminal nociceptive inputs inhibit vagal-parasympathetic reflex vasodilation in the masseter muscle and suggest that the activation of GABA(B) rather than GABA(A) receptors underlies the observed inhibition in the NTS.  相似文献   

12.
J Hubbard  N Sirett  J Sibbald 《Life sciences》1989,45(18):1715-1719
Althesin and pentobarbitone are anaesthetics which act by prolonging the open time of the chloride channels of the GABA(A) receptor. To explain why luteinizing hormone (LH) release is less depressed by Althesin anaesthesia than by pentobarbitone anaesthesia we suggest that either Althesin is a less potent anaesthetic in the preoptic area or that Althesin as well as stimulating GABA(A) receptors has some other action, perhaps stimulation of GABA(B) receptors, which may facilitate LH release. To investigate the relative potency of the anaesthetics in the preoptic area nine cats were anaesthetised, six with Althesin and three with pentobarbitone, mounted in a stereotaxic frame and prepared for extracellular recording and stimulation of spontaneously active units in the preoptic region. When cats anaesthetised with Althesin were compared with cats anaesthetised with pentobarbitone there were significantly fewer of these units for the number of tracks made. These units also had a significantly lower frequency and a distribution significantly skewed toward lower frequencies. Electrical stimulation of the fornix and of sites in the medial basal hypothalamus and medial forebrain bundle inhibited about 50% of the units and the median duration of the inhibitory pause was significantly longer following stimulation at all three sites in cats anaesthetised with Althesin. We conclude that Althesin is a more potent anaesthetic than pentobarbitone in the preoptic region and that its effects on LH release cannot be explained by its effects on the GABA(A) receptor alone.  相似文献   

13.
To examine the role of gamma-aminobutyric acid (GABA)(A) receptor mediating systems in the control of gonadotropin-releasing hormone (GnRH) release from the medial preoptic area (MPOA) of ewes during the follicular phase of the estrous cycle, the extracellular concentrations of GnRH, beta-endorphin, noradrenaline (NE), dopamine (DA), 4-hydroxy-3-methoxy-phenyl-glycol (MHPG) and 3,4-dihydroxy-phenylacetic acid (DOPAC) were quantified during the local infusion of muscimol and bicuculline (agonist and antagonist of GABA(A) receptors, respectively) to this structure. Stimulation of GABA(A) receptors markedly attenuated GnRH release, increased beta-endorphin release and noradrenergic system activity in the MPOA. The decrease of the luteinizing hormone (LH) concentration in blood plasma and LH pulse amplitude suggests that a GABA(A) receptor agonist in the MPOA also suppresses GnRH release from the GnRH axon terminals in the ventromedial hypothalamus/nucleus infundibularis region (VEN/NI). Blockade of GABA(A) receptors had no evident effect on GnRH/LH secretion but decreased beta-endorphin release and increased the extracellular DOPAC concentration. The suppressive influence of muscimol in the MPOA on GnRH release might be considered a net result of its direct inhibitory effect on GnRH release, indirect inhibitory influence on GnRH release through activation of the beta-endorphinergic system, and facilitation of GnRH neurons by increasing noradrenaline release. The results obtained during bicuculline perfusion on these systems' activity are not sufficiently consistent to provide a clear understanding of the lack of changes in the GnRH/LH release under blockade of GABA(A) receptors. We conclude that the MPOA in ewes during the follicular phase is an important regulatory site where stimulation of GABA(A) receptors both decreases GnRH secretion and increases beta-endorphin release.  相似文献   

14.
Magnusson AK  Park TJ  Pecka M  Grothe B  Koch U 《Neuron》2008,59(1):125-137
Central processing of acoustic cues is critically dependent on the balance between excitation and inhibition. This balance is particularly important for auditory neurons in the lateral superior olive, because these compare excitatory inputs from one ear and inhibitory inputs from the other ear to compute sound source location. By applying GABA(B) receptor antagonists during sound stimulation in vivo, it was revealed that these neurons adjust their binaural sensitivity through GABA(B) receptors. Using an in vitro approach, we then demonstrate that these neurons release GABA during spiking activity. Consequently, GABA differentially regulates transmitter release from the excitatory and inhibitory terminals via feedback to presynaptic GABA(B) receptors. Modulation of the synaptic input strength, by putative retrograde release of neurotransmitter, may enable these auditory neurons to rapidly adjust the balance between excitation and inhibition, and thus their binaural sensitivity, which could play an important role as an adaptation to various listening situations.  相似文献   

15.
Pallidal dopamine, GABA and the endogenous opioid peptides enkephalins have independently been shown to be important controllers of sensorimotor processes. Using in vivo microdialysis coupled to liquid chromatography-mass spectrometry and a behavioral assay, we explored the interaction between these three neurotransmitters in the rat globus pallidus. Amphetamine (3 mg/kg i.p.) evoked an increase in dopamine, GABA and methionine/leucine enkephalin. Local perfusion of the dopamine D(1) receptor antagonist SCH 23390 (100 μM) fully prevented amphetamine stimulated enkephalin and GABA release in the globus pallidus and greatly suppressed hyperlocomotion. In contrast, the dopamine D(2) receptor antagonist raclopride (100 μM) had only minimal effects suggesting a greater role for pallidal D(1) over D(2) receptors in the regulation of movement. Under basal conditions, opioid receptor blockade by naloxone perfusion (10 μM) in the globus pallidus stimulated GABA and inhibited dopamine release. Amphetamine-stimulated dopamine release and locomotor activation were attenuated by naloxone perfusion with no effect on GABA. These findings demonstrate a functional relationship between pallidal dopamine, GABA and enkephalin systems in the control of locomotor behavior under basal and stimulated conditions. Moreover, these findings demonstrate the usefulness of liquid chromatography-mass spectrometry as an analytical tool when coupled to in vivo microdialysis.  相似文献   

16.
Cerebellar granule neurons can be conveniently kept in culture. They constitute a useful model to study regulation of glutamatergic activity, in particular the inhibitory action of GABA (7-aminobutyrate). GABA exerts an inhibitory action on evoked transmitter release acting on both GABA(A) and GABA(B) receptors. The functional properties of these receptors are dependent upon the environment of the neurons during early development in culture as the expression of both receptor subtypes is enhanced by exposure of the neurons to GABA(A) receptor agonists. Thus, the inducible GABA(A) receptors are of low affinity and lack benzodiazepine sensitivity, and the G-protein coupling differs among the native and the inducible GABA(B) receptors. Moreover, the GABA(A) and the GABA(B) receptors are functionally coupled, leading to a disinhibitory action of GABA. Therefore drugs exhibiting selective agonist or antagonist action on subclasses of GABA(A) and GABA(B) may be of potential use as regulators of glutamatergic excitatory activity.  相似文献   

17.
GABA(B) receptor subunits are widely expressed on neurons throughout the central nervous system (CNS), at both pre- and postsynaptic sites, where they mediate the late and slow component of the inhibitory response to the major inhibitory neurotransmitter GABA. Recently, GABA(B) receptors have been reported to be expressed in astrocytes and microglia in the rat CNS by immunocytochemistry. However, there are few reports available for the functional characterization of GABA(B) receptors on astrocytes. In the present study, we therefore investigated the functional expression and characteristics of GABA(B) receptors in primary cultures of astrocytes from rat cerebral cortex. In the presence of 10 microM GTP, forskolin concentration-dependently increased adenylylcyclase (AC) activity in membranes prepared from rat astrocytes. The selective GABA(B) agonist (R)-baclofen concentration-dependently reduced forskolin-stimulated AC activity in the presence of 10 microM GTP. This effect was reversed by the selective GABA(B) antagonists, CGP-55845 and CGP-54626, and was completely abolished by treatment of astrocytic membranes with pertussis toxin. In addition, RT-PCR, Western blotting, and immunocytochemistry clearly showed that metabotropic GABA(B) receptor isoforms (GABA(B)R1 and GABA(B)R2) are expressed in rat cerebrocortical astrocytes. Taken collectively, these results demonstrate that functionally active metabotropic GABA(B) receptors are expressed in rat cerebrocortical astrocytes.  相似文献   

18.
Prior investigations have shown that localized infusion by microdialysis of gamma-aminobutyric acid(B) (GABA(B)) agonists into the medial basal hypothalamus of male sheep rapidly increases GnRH and LH pulse amplitude. The objectives of these studies were to determine if infusion of GABA(B) agonists SKF 97541 or baclofen into the medial basal hypothalamus of female sheep would affect basal LH secretion and if infusion of a potent antagonist would alter expression of LH surges induced by injection of estrogen. Infusion of either SKF 97541 (10 or 40 microM) or baclofen (1 mM) into estrogen-treated ovariectomized ewes did not alter basal LH secretory patterns, whereas both drugs significantly elevated mean LH and LH pulse amplitude in ovariectomized ewes during the nonbreeding season. Infusion of the antagonist CGP 52432 (250 or 500 microM) did not affect expression of estrogen-induced LH surges in ovariectomized ewes. These observations support the concept that GABA(B) receptors in the medial basal hypothalamus regulate basal LH secretion but do not regulate the surge mode of LH secretion in the female sheep.  相似文献   

19.
Prenatal exposure to diazepam (DZ), a positive allosteric modulator of the gamma-aminobutyric acid(A) (GABA(A)) receptor complex, exerts profound effects that become more evident during puberty and in many cases are sex-specific, suggesting that such exposure interferes with the activity of steroid hormones. Apart from their well known effects on the genome, the reduced metabolites of many steroid hormones also interact directly with membrane receptors, including those for N-methyl-D-aspartate (NMDA). In this study, we compared the effects of several neurosteroids on NMDA receptors from normal rats and those exposed in utero to DZ (1.25mg/kg per day) from the 14th through the 20th day of gestation.In superfused rat hippocampal synaptosomes, activation of the NMDA receptor stimulates the basal release of [3H]noradrenaline ([3H]NA), which was used in our study as an index of receptor function. [3H]NA release was evoked in a concentration-dependent manner by NMDA (100 microM) plus glycine (GLY). The maximal increase (68.23+/-3.86%) with respect to basal release was achieved with a GLY concentration of 10 microM, and the EC(50) for GLY was 0.1 microM. Release stimulated by 100 microM NMDA + 0.1 microM GLY was not modified by any of the neurosteroids tested, with the exception of pregnenolone sulfate (PREG-S), which produced a 78.57+/-3.94% reduction in release at the maximal concentration used (0.3 microM). In synaptosomes from animals exposed in utero to DZ, the inhibitory effect of PREG-S was reduced by 46.55+/-2.33%.Given the important roles played by NMDA receptors in physiological and pathological processes within the central nervous system (CNS), characterization of NMDA receptor modulation is an important objective. The fact that this modulation can be altered by exposure in utero to DZ indicates that the behavioral abnormalities observed in exposed animals might be partially attributed to an altered sensitivity of NMDA receptors to the modulatory effects of neurosteroids.  相似文献   

20.
Corticotropin-releasing factor (CRF) and the urocortins (UCNs) are structurally and pharmacologically related neuropeptides which regulate the endocrine, autonomic, emotional and behavioral responses to stress. CRF and UCN1 activate both CRF receptors (CRFR1 and CRFR2) with CRF binding preferentially to CRFR1 and UCN1 binding equipotently to both receptors. UCN2 and UCN3 activate selectively CRFR2. Previously an in vitro study demonstrated that superfusion of both CRF and UCN1 elevated the GABA release elicited by electrical stimulation from rat amygdala, through activation of CRF1 receptors. In the present experiments, the same in vitro settings were used to study the actions of CRF and the urocortins on hypothalamic GABA release. CRF and UCN1 administered in equimolar doses increased significantly the GABA release induced by electrical stimulation from rat hypothalamus. The increasing effects of CRF and UCN1 were inhibited considerably by the selective CRFR1 antagonist antalarmin, but were not influenced by the selective CRFR2 antagonist astressin 2B. UCN2 and UCN3 were ineffective. We conclude that CRF1 receptor agonists induce the release of GABA in the hypothalamus as well as previously the amygdala. We speculate that CRF-induced GABA release may act as a double-edged sword: amygdalar GABA may disinhibit the hypothalamic CRF release, leading to activation of the hypothalamic-pituitary-adrenal axis, whereas hypothalamic GABA may inhibit the hypothalamic CRF release, terminating this activation.  相似文献   

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