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1.
The mu (μ) opioid receptors, which mediate the effects of morphine, are widely distributed in brain. We have examined the distribution of mRNA encoding a μ opioid receptor in rat brain with in situ hybridization histochemistry at the single-cell level to obtain information about the cell types synthesizing this receptor. Only neurons, not glia, were labeled in discrete brain regions. High levels of labeling were detected in the thalamus, striosomes of the caudateputamen, globus pallidus, and brain regions involved in nociception, arousal, respiratory control, and, possibly, addiction. The general distribution of the receptor mRNA paralleled that of μ opioid binding sites with some notable exceptions. These include the cerebral cortex, which contains binding sites, but very few labeled neurons. No labeling was observed in the cerebellum, a region devoid of μ binding sites. Three main findings emerged from these experiments: (1) the mRNA was present in regions mediating both the therapeutic (analgesia) and the unwanted (respiratory depression, addiction) effects of morphine, (2) the mRNA was very densely expressed by neurons known to receive dense enkephalin-containing inputs, and (3) the dissociation between the presence of binding sites and absence of mRNA in some brain regions supports a presynaptic localization of μ opioid receptors in these areas. Alternatively, other subtypes of μ opioid receptors may be encoded by a different mRNA. These results provide new insights into the receptor types and neuronal circuits involved in the effects of endogenous opioids and morphine. © 1994 Wiley-Liss, Inc.  相似文献   

2.
Cultures of aggregating fetal rat brain cells express mu, delta, and kappa opioid receptors. The potent and long-lasting opioid antagonist naltrexone was used to investigate whether different regulatory mechanisms are involved in the expression of the three receptor subtypes. In cultures treated for seven days, naltrexone increased dose-dependently the binding of 3H-diprenorphine to the three receptor subtypes, with the mu sites being affected at a lower concentration than the other two; A Scatchard analysis indicated that this receptor up-regulation was obtained by an increase in the BMax, with no significant change in the affinity of the ligand to the receptors. In contrast to these effects in cultures treated for 7 days, it was surprising to find that a 48 hr treatment with naltrexone had an apparent converse and subtype-specific influence; the antagonist decreased significantly the binding of 3H-diprenorphine to both mu and delta receptors but had no effect on kappa sites. Two other opioid antagonists, naloxone and levallorphan, had a similar effect. Further analysis of naltrexone's mode of action was obtained by studying its effect on the adenylate cyclase activity. Of several inducers of this enzyme, the beta-adrenergic inducer isoproterenol gave the highest increase in cyclic AMP. Naltrexone had no significant effect on the basal adenylate cyclase activity but it altered the pattern of cyclic AMP formation in isoproterenol-stimulated cultures. Overall, the results indicate that in addition to its classic antagonistic activity, naltrexone exhibits in fetal brain aggregates some properties associated with opiate agonists.  相似文献   

3.
The distribution of the mRNA for a pituitary adenylate cyclase-activating polypeptide (PACAP) receptor (PACAP-R) was examined in the rat brain, and also in the hypophysis and pineal gland, by in situ hybridization with a specific 35S-labeled riboprobe which was generated from a rat PACAP-R cDNA clone. In the brain, expression of PACAP-R mRNA was most prominent in the periglomerular and granule cells of the olfactory bulb, granule cells of the dentate gyrus, supraoptic nucleus, and area postrema. The expression was also intense in the piriform, cingulate, and retrosplenial cortices, pyramidal cells in CA2, non-pyramidal cells in CA1-CA3, neuronal cells in the hilus of the dentate gyrus, lateral septal nucleus, intercalated amygdaloid nucleus, anterodorsal thalamic nucleus, most of the midline and intralaminar thalamic nuclei, many regions of the hypothalamus, dorsal motor nucleus of the vagus nerve, hypoglossal nucleus, and lateral reticular nucleus. No significant expression was detected in the mitral and tufted cells in the olfactory bulb, pyramidal cells in CA1 and CA3, posterior nuclear group of the thalamus, dorsal lateral geniculate nucleus, and Purkinje, Golgi, and granule cells in the cerebellar cortex. Moderate-to-weak expression was further observed in many other regions of the brain. In the cerebellar cortex, presumed Bergmann glia cells showed moderate expression. In the hypophysis, the expression was moderate in the anterior lobe, and weak to moderate in the posterior lobe; no significant expression was observed in the intermediate lobe. In the pineal gland, the expression was very weak, if any. Thus, the expression of PACAP-R was detected not only on neuronal cells but also on some particular glial cells. The present study has shown, for the first time, the exact site of PACAP-R expression in the brain and hypophysis. Although the functional significance of PACAP and PACAP-R in the brain still remains to be clarified, the present results are considered to provide some direction for future functional studies. © 1996 Wiley-Liss, Inc.  相似文献   

4.
To assess the validity of rodent models for investigating the role of delta opioid receptors (DOR) in analgesia, the distribution of DOR binding and mRNA were compared between rodent and primate spinal cord and dorsal root ganglia (DRG), using receptor autoradiography and in situ hybridization, respectively. In mouse and rat spinal cord, [(125)I]-deltorphin-labeled DOR binding sites were detected throughout the gray matter. In contrast, in primate and particularly in human spinal cord, DOR binding was mainly present in laminae I-II, with little to no binding in deeper layers. Accordingly, in rodent spinal cord, DOR mRNA was expressed by a large number of neurons distributed throughout the ventral and dorsal horns, whereas in the primate, DOR expression was significantly lower, as evidenced by a moderate number of labeled cells throughout the gray matter in monkey and by only few labeled cells in human, mainly in Clarke's column and lamina IX. Major species differences in DOR expression were also observed in primary afferent cells bodies. In rat DRG, intense DOR mRNA hybridization was primarily observed over large ganglion cells immunopositive for neurofilament 200. In contrast, in monkey and human DRG, DOR mRNA was primarily detected over small and medium-sized ganglion cells. These results demonstrate major differences in the expression and distribution of DOR in the spinal cord and DRG between mammalian species. Specifically, they point to a progressive specialization of DOR toward the regulation of primary somatosensory, namely nociceptive, inputs during phylogeny and suggest that the effects of DOR agonists in rodents may not be entirely predictive of their action in humans.  相似文献   

5.
Concomitant abuse of buprenorphine (BPN) and benzodiazepines (BZD) may relate to a pharmacodynamic interaction between the two. The objective of the present work was to investigate the acute and chronic effects of clorazepate (CRZ) alone or in combination with BPN on selective kappa opiate tritiated ligand [3H]-U69 593 and delta opiate radioligand [3H]-deltorphine II binding in the rat brain. Bmax (maximal receptor density) and Kd (the dissociation constant) were directly determined at different brain regions of interest (ROI) selected for high densities of kappa and/or delta receptors in rats treated with BPN and/or CRZ. The agents were administered either once or for 21 consecutive days. Differences in Bmax and Kd (for both specific ligands) were related to drug treatment and receptor location. Globally, single BPN administration induced no changes in kappa or delta opiate receptor binding, whereas repeated BPN administration up-regulated kappa receptor density and decreased delta affinity. At the kappa receptor level, repeated administration of CRZ acted only on Kd, whereas the delta receptor was up-regulated. Repeated addition of CRZ to BPN had no effect on kappa receptor Bmax versus chronic controls. By significantly decreasing Bmax, CRZ nullified the effect of chronic BPN on the kappa receptor. The modifications were strongest in the nucleus accumbens, where both types of receptor occur. Treatments had region-selective effects in some brain areas, such as the amygdala, periaqueductal gray matter, hypothalamus and caudate putamen. Increased mu and delta receptor densities would be expected to provide reinforcement by enhancing reward, and impairment of kappa receptor availability would be expected to decrease aversion. The effects described are likely to influence addictive behavior among people abusing BZD and BPN.  相似文献   

6.
Opioid receptor agonists induce noradrenaline release in the supraspinal, spinal, and peripheral sites. Endogenous noradrenaline release can induce an antinociceptive effect by activation of the α(2) adrenoceptor. This interaction between the opioid and the adrenergic systems could be the alternative mechanism by which opioid receptor agonists mediate peripheral antinociception. Therefore, the aim of the present study was to verify whether peripheral antinociception induced by the μ, δ, and κ opioid receptor agonists DAMGO, SNC80, and bremazocine, respectively, through the endogenous noradrenergic system. All drugs were administered locally into the right hind paw of male Wistar rats. The rat paw pressure test was used, with hyperalgesia induced by intraplantar injection of prostaglandin E(2). DAMGO, SNC80, or bremazocine elicited local dose-dependent peripheral antinociception. This peripheral effect was antagonized by the nonselective α(2) adrenoceptor antagonist yohimbine and by the selective α(2C) adrenoceptor antagonist rauwolscine but not by the selective antagonists for α(2A), α(2B), and α(2D) adrenoceptor subtypes (BRL 44 480, imiloxan, and RX 821002, respectively). The opioid-induced effect was antagonized by the nonselective α(1) adrenoceptor antagonist prazosin and by the nonselective β adrenoceptor antagonist propranolol. Guanethidine, a depletor of peripheral sympathomimetic amines, restored approximately 50-60% of the opioid-induced peripheral antinociception. Furthermore, acute injection of the noradrenaline reuptake inhibitor reboxetine intensified the antinociceptive effects of low-dose DAMGO, SNC80, or bremazocine. This study provides evidence that DAMGO, SNC80, or bremazocine induces peripheral antinociception by noradrenaline release and interaction with adrenoceptors.  相似文献   

7.
We have examined responses of mice lacking mu, delta and kappa opioid receptor (MOR, DOR and KOR, respectively) genes, as well as combinatorial mutants, in several pain models. This is the first truly comparative study of all three opioid receptor-deficient mice, with genotypes and gender analysis using mice on the hybrid 50% 129/SV : 50% C57BL/6 genetic background. In the tail-immersion test, only KOR-/- females showed decreased withdrawal latencies. This modification was also found in MOR/KOR and MOR/DOR/KOR, but not MOR/DOR mutants. The hotplate test revealed increased nociceptive sensitivity for MOR-/-, a phenotype which was also observed in double mutants involving the MOR deletion, and in the triple mutants. The tail-pressure test showed increased response for both MOR-/- and DOR-/- mutants, a modification which was enhanced in the triple-mutant mice. In the formalin test, MOR-/- and DOR-/- mice showed increased responses in the early and late phases, respectively, while the triple mutant tended to show enhanced nociception in both phases. Finally, the enhanced response of KOR-/- mice in the writhing test, which we have demonstrated previously, was confirmed in double MOR/KOR- and triple-mutant mice. Together, the data support the existence of an antinociceptive opioid tone. Each receptor presents a distinct pattern of activities, with mu receptors influencing responses to mechanical, chemical and thermal nociception at a supraspinal level, kappa receptors involved in spinally mediated thermal nociception and chemical visceral pain, and delta receptors modulating mechanical nociception and inflammatory pain. Phenotypes of mutant mice were subtle, suggesting a low endogenous opioid tone in the regulation of physiological pain.  相似文献   

8.
The distribution of cells that express mRNA encoding the androgen (AR) and estrogen (ER) receptors was examined in adult male and female rats by using in situ hybridization. Specific labeling appeared to be largely, if not entirely, localized to neurons. AR and ER mRNA-containing neurons were widely distributed in the rat brain, with the greatest densities of cells in the hypothalamus, and in regions of the telencephalon that provide strong inputs in the medial preoptic and ventromedial nuclei, each of which is thought to play a key role in mediating the hormonal control of copulatory behavior, as well as in the lateral septal nucleus, the medial and cortical nuclei of the amygdala, the amygdalohippocampal area, and the bed nucleus of the stria terminalis. Heavily labeled ER mRNA-containing cells were found in regions known to be involved in the neural control of gonadotropin release, such as the anteroventral periventricular and the arcuate nuclei, but only a moderate density of labeling for AR mRNA was found over these nuclei. In addition, clearly labeled cells were found in regions with widespread connections throughout the brain, including the lateral hypothalamus, intralaminar thalamic nuclei, and deep layers of the cerebral cortex, suggesting that AR and ER may modulate a wide variety of neural functions. Each part of Ammon's horn contained AR mRNA-containing cells, as did both parts of the subiculum, but ER mRNA appeared to be less abundant in the hippocampal formation. Moreover, AR and ER mRNA-containing cells were also found in olfactory regions of the cortex and in both the main and accessory olfactory bulbs. AR and ER may modulate nonolfactory sensory information as well since labeled cells were found in regions involved in the central relay of somatosensory information, including the mesencephalic nucleus of the trigeminal nerve, the ventral thalamic nuclear group, and the dorsal horn of the spinal cord. Furthermore, heavily labeled AR mRNA-containing cells were found in the vestibular nuclei, the cochlear nuclei, the medial geniculate nucleus, and the nucleus of the lateral lemniscus, which suggests that androgens may alter the central relay of vestibular and auditory information as well. However, of all the regions involved in sensory processing, the heaviest labeling for AR and ER mRNA was found in areas that relay visceral sensory information such as the nucleus of the solitary tract, the area postrema, and the subfornical organ. We did not detect ER mRNA in brainstem somatic motoneurons, but clearly labeled AR mRNA-containing cells were found in motor nuclei associated with the fifth, seventh, tenth, and twelfth cranial nerves. Similarly, spinal motoneurons contained AR but not ER mRNA.(ABSTRACT TRUNCATED AT 400 WORDS)  相似文献   

9.
The mRNA expression for preprotachykinin-A (PPT-A) was studied throughout the human and cynomolgus monkey brain to assess the neuroanatomical expression pattern of the PPT-A gene in primates. In situ hybridization showed that the PPT-A mRNA is expressed highly in specific regions of the postmortem human brain, including the striatum, islands of Calleja, hypothalamus (posterior, premammillary, medial mammillary, and ventromedial nuclei), superior and inferior colliculi, periaqueductal gray, and oculomotor nuclear complex. PPT-A mRNA-expressing neurons also were present in the paranigralis (ventral tegmental area) and were scattered in the bed nucleus stria terminalis throughout the sublenticular substantia innominata region, including the diagonal band of Broca and the nucleus basalis of Meynert. In the hippocampus, high PPT-A mRNA expression was localized predominantly to the polymorphic layer of the dentate gyrus; no labeled cells were present in the granular layer. Positively labeled cells also were found scattered in the CA regions as well as in the amygdaloid complex. Neocortical expression of PPT-A mRNA was localized mainly to the deep laminae (layers V/VI), except for the striate cortex (labeling was seen also in superficial layers). The subiculum, thalamus, globus pallidus, ventral pallidum, substantia nigra pars compacta, red nucleus, pontine nuclei, and cerebellum were characterized by very weak to undetectable expression of PPT-A mRNA. An expression pattern was evident in the monkey forebrain similar to that observed in the human, except for the absence of PPT mRNA-expressing cells in the medial mammillary nucleus despite intense expression in supramammillary, lateral mammillary, and premammillary nuclei. Overall, more similarities than differences are apparent between primate species in the expression pattern of the PPT-A gene. J. Comp. Neurol. 411;56-72, 1999.  相似文献   

10.
D-Ala2, D-Leu5-enkephalin (DADLE) and dynorphin1-13 (Dyn1-13) inhibited striatal adenylate cyclase activity, both basal and dopamine-stimulated (DA), in rats and guinea pigs. The kappa-agonists bremazocine (BRZ), U-50,488 (trans-3,4-dicloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]- benzeneacetamide), and U-69,593 (5 alpha, 7 alpha 8 beta)-(-)-N-methyl-N-(7-(1-pyrrolidinyl-1-oxaspiro (4.5)dec-8yl) benzeneacetamide inhibited only the basal adenylate cyclase activity, and such an effect was restricted to guinea pig striatum, an area known to contain a high density of kappa-binding sites. Moreover, BRZ was found to antagonize the inhibitory effect of both DADLE and Dyn1-13 in rat striatum.  相似文献   

11.
Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the mammalian central nervous system. GABA exerts its actions through two classes of receptors: GABA(A), multimeric ligand-gated Cl(-) ion channels (a class which has been proposed to include the homomeric variant previously called GABA(C), to be designated GABA(A0r)); and GABA(B), G-protein coupled receptors which regulate Ca(2+) and K(+) channels. Currently, within the GABA(B) receptor family two proteins have been identified through molecular cloning techniques and designated GABA(B1) and GABA(B2). Two N-terminal variants of GABA(B1) were isolated and designated GABA(B1a) and GABA(B1b). The distribution of neurons in the rat CNS expressing the mRNA for the GABA(B1) isoforms have been previously described by in situ hybridization histochemistry. The recent isolation and identification of the GABA(B2) protein by homology cloning has enabled the use of radiolabeled oligonucleotides to detect the distribution of the expression of GABA(B2) mRNA in the rat CNS. The expression of GABA(B2) mRNA was observed to be primarily related to neuronal profiles. The highest levels of GABA(B2) mRNA expression were detected in the piriform cortex, hippocampus, and medial habenula. GABA(B2) mRNA was abundant in all layers of the cerebral cortex, the thalamus and in cerebellar Purkinje cells. Moderate expression was observed in several hypothalamic and brainstem nuclei. In contrast to the distribution of GABA(B1) mRNA, only a weak hybridization signal for GABA(B2) was detected over cells of the basal ganglia, including the caudate-putamen, nucleus accumbens, olfactory tubercle and throughout most of the hypothalamus. Moderate-to-heavy GABA(B2) mRNA expression was also seen over dorsal root and trigeminal ganglion cells. In general, the pattern of GABA(B2) mRNA expression in the rat brain overlaps considerably with the distributions described for both GABA(B1) mRNAs, and is concordant with the distribution described for GABA(B) receptor binding sites. However, differences between GABA(B2) expression levels and GABA(B) binding sites were observed in the basal ganglia.  相似文献   

12.
While the distribution of opioid receptors can be differentiated in the rat central nervous system, their precise localization has remained controversial, due, in part, to the previous lack of selective ligands and insensitive assaying conditions. The present study analyzed this issue further by examining the receptor selectivity of [3H]DAGO (Tyr-D-Ala-Gly-MePhe-Gly-ol), [3H]DPDPE (2-D-penicillamine-5-D-penicillamine-enkephalin), [3H]DSLET (Tyr-D-Ser-Gly-Phe-Leu-Thr) and [3H](-)bremazocine, and their suitability in autoradiographically labelling selective subpopulations of opioid receptors in rat brain. The results from saturation, competition, and autoradiographic experiments indicated that the three opioid receptor subtypes can be differentiated in the rat brain and that [3H]DAGO and [3H]DPDPE selectively labelled mu and delta binding sites, respectively. In contrast, [3H]DSLET was found to be relatively non-selective, and labelled both mu and delta sites. [3H]Bremazocine was similarly non-selective in the absence of mu and delta ligands and labelled all three opioid receptor subtypes. However, in the presence of 100 nM DAGO and DPDPE, concentrations sufficient to saturate the mu and delta sites, [3H]bremazocine did label kappa sites selectively. The high affinity [3H]bremazocine binding sites showed a unique distribution with relatively dense kappa labelling in the hypothalamus and median eminence, areas with extremely low mu and delta binding. These results point to the selectivity, under appropriate conditions, of [3H]DAGO, [3H]DPDPE and [3H]bremazocine and provide evidence for the differential distribution of mu, delta, and kappa opioid receptors in rat brain.  相似文献   

13.
Mu opioid receptors (MOR) are known to be involved in seizure activity. The main goal of the present study was to characterize the MOR mRNA expression, binding, as well as G protein activation mediated by these receptors in epileptic hippocampus of patients with pharmacoresistant mesial temporal lobe epilepsy (TLE). In contrast with autopsy samples, hippocampus obtained from patients with mesial TLE demonstrated enhanced MOR mRNA expression (116%). Saturation binding experiments revealed significantly higher (60%) B(max) values for the mesial TLE group, whereas the K(d) values were not statistically different. Although mesial TLE group demonstrated high levels of basal binding for the G proteins (136%), DAMGO-stimulated [(35)S]GTPγS binding did not demonstrate significant alterations. In conclusion, our present data provide strong evidence that the epileptic hippocampus of patients with pharmacoresistant mesial TLE presents significant alterations in MOR. Such changes may represent adaptive mechanisms to compensate for other as yet unknown alterations.  相似文献   

14.
We have investigated the effects of specific mu-, kappa-and delta-opioid receptor agonists and antagonists on the hypothalamic noradrenergic neurotransmission and on luteinising hormone (LH) release in the ovariectomised and steroid-primed rat. The opioid agents were infused intracerebroventricularly under ketamine anaesthesia and blood samples collected at hourly intervals on the afternoon of the anticipated LH surge. At the end of the experiment, the rats were decapitated and the medial preoptic area, suprachiasmatic nucleus, median eminence and arcuate nucleus surgically isolated by micropunch. The concentrations of noradrenaline (NA) and its metabolite (3,4-dihydroxyphenylglycol; DHPG) in these samples was determined by high performance liquid chromatography with electrochemical detection. Plasma LH levels were measured by radioimmunassay. The three opioid agonists reduced concentrations of NA and DHPG in all four hypothalamic areas. These inhibitory effects of the opioid agonists were mostly prevented following coadministration with their respective antagonists. However, naloxone had no significant effect on DHPG levels in any of the hypothalamic regions examined. Plasma LH levels were found to be either low or undetectable in all groups. These results suggest that mu-, kappa- and delta-opioid receptors have inhibitory influence on the hypothalamic noradrenergic neurotransmission around the time of the LH surge. It is thought that the ketamine anaesthesia interfered with LH release.  相似文献   

15.
We determined the effects of morphine on mRNA levels for the opioid ligands preprodynorphin (PPD) and preproenkephalin (PPE) and the kappa opioid receptor (KOR). Rats received six injections of morphine (6.25 mg/kg/injection) every 2 h, and were sacrificed 30 min later. mRNA levels were measured in brain tissue after removal of the cortex, cerebellum and brainstem. There were increases in PPD and KOR mRNA levels (P<0.05 and P<0.005, respectively), with no alteration of PPE. These alterations in the kappa/dynorphin system may counter morphine-induced effects on the brain.  相似文献   

16.
Interleukin-1 (IL-1) exerts a wide variety of biological effects on various cell types and may be regarded as a pleiotropic peptide hormone. Biological evidence suggests that IL-1 participates in the modulation of central nervous system physiology and behaviour in a fashion characteristic of neuroendocrine hormones. In this investigation, recombinant (r) human (h) IL-1 and r mouse (m) IL-1 were examined for their modulation of opioid peptide receptor binding in vitro. Experiments were performed on frozen sections of rat brain. Receptor binding of radiolabeled substance P and of radiolabeled neurotensin were not significantly affected by the presence of rIL-1s. Recombinant IL-1s, however, significantly enhanced specific binding of 125I-beta-endorphin (125I-beta-END) and of D-ala2-(tyrosyl-3,5-3H)enkephalin-(5-D-leucine) (3H-D-ALA), equipotently and in a concentration-dependent manner with maximal activity occurring at a concentration of 10 LAF units/ml. The increased binding of 125I-beta-END and 3H-D-ALA was blocked steroselectively by (-)-naloxone and by etorphine, suggesting detection of opiate receptors. In addition, brain distribution patterns of receptors labeled in the presence of rIL-1s corresponded to patterns previously published for opiate receptors. Autoradiographic visualization of receptors revealed that rIL-1s in the different areas of the brain exert their effect on opioid binding with comparable potencies. The data suggest that certain central nervous system effects of IL-1s may be mediated by their selective interaction with opiatergic systems at the receptor level.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

17.
Opioid receptor proteins and mRNAs have been localized to a variety of regions within the rat brain. It is generally accepted that within the lobes of the rat cerebellum, only delta opioid receptor (DOR) is expressed. This is in contrast to that observed in humans and rabbits which express both mu opioid receptor (MOR) and DOR. In this study, we report detection of MOR as well as DOR protein by immunohistochemical localization, and mRNA by fluorescent in situ hybridization (FISH) within Purkinje cells (PK) and the granular layer of neonatal (P6) and adult rat cerebellum. Expression of MOR mRNA was also detected within cells of the molecular layer, but at lower levels than those seen within the PK cells. Abundant expression of MOR and DOR mRNA was detected in the external germinal layer of the immature cerebellum of the fetal (E16) rat, supporting a role for MOR and DOR in regulating neurogenesis of the cerebellum. In addition, using exon-specific cRNA probes, exons 1 and 4, which are both found in the MOR-1 splice variant mRNA, were detected in PK cells in the cerebellum and also within deep cerebellar nuclei in the adult.  相似文献   

18.
Antisense digoxigenin-labeled deoxyoligonucleotides probes and non-isotopic in situ hybridization (HIS) techniques have been used to explore the NMDA-NR1 receptor subunit mRNA distribution in different brain areas of rats which had their dopaminergic nigrostriatal pathway previously lesioned with intracerebral administration of 6-OH-dopamine (6-OH-DA). Intense and significant hybridization signals for NR1 mRNA were found in dentate gyrus and regions CA1-CA2-CA3 of the hippocampus, in layers II-III and V-VI of the cerebral cortex, and in the cerebellum of sham-treated rats. Basal ganglia structures such as the striatum exhibited few NR1 mRNA hybridization signals as compared to the hippocampus and cerebral cortex. In contrast, both zona compacta and reticulata of substantia nigra (SN) showed a reduced number of cells with nevertheless intense NR1 mRNA HIS signals. The NR1 mRNA distribution in the brain was affected in a brain regional selective manner by 6-OH-DA induced lesions of DA neuronal systems. A striking increase in NR1 mRNA HIS signals was observed in both striata after unilateral lesioning with 6-OH-DA. Instead, in SN compacta but not in reticulata, a moderate but significant bilateral reduction of NR1 mRNA was observed after unilateral 6-OH-DA injection. No significant changes in NR1 mRNA were detected in cerebral cortex and other brain regions after 6-OH-DA treatment. These studies, and others reported in the literature, support the view that extensive lesions of nigrostriatal DA-containing neurons in the brain may trigger compensatory or adaptative responses in basal ganglia structures such as striatum and substantia nigra which involve glutamatergic neurons and the genic expression of NMDA receptors. © 1996 Wiley-Liss, Inc.  相似文献   

19.
We investigated the ability of selective opioid agonists and antagonists to influence pro-opiomelanocortin peptide secretion from the rat neurointermediate lobe in vitro. The mu-opioid agonist DAMGO ([D-Ala(2), N-Me-Phe(4), Gly(5)-ol]enkephalin) significantly stimulated beta-endorphin and alpha-melanocyte-stimulating hormone release relative to controls early (30 min) in the incubation period. Similar effects on beta-endorphin secretion were observed with the selective mu-opioid agonist dermorphin. The delta-opioid receptor agonist DPDPE ([D-Pen(2,5)]enkephalin) weakly inhibited beta-endorphin secretion relative to controls while the kappa-opioid receptor agonist U50488 had no effect. The mu-opioid selective antagonist CTOP (D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH(2)) inhibited basal beta-endorphin secretion while kappa- and delta-opioid receptor antagonists had no effect. Our data support a role for local mu-opioid receptor control of intermediate lobe pro-opiomelanocortin peptide secretion. Peptide secretion from melanotropes appears to be tonically stimulated by activation of mu-opioid receptors in the absence of intact neuronal innervation to the intermediate lobe.  相似文献   

20.
The radioautographic distribution of mu, delta and kappa opioid binding sites was examined by in vitro radioautography in the rat hypothalamus using the highly selective ligands [125I]-FK 33-824, [125I]azidoDTLET and [125I]DPDYN, respectively. Levels of mu opioid binding sites varied considerably amongst hypothalamic nuclei. mu Opioid labeling was dense in the medial preoptic area, medial preoptic nucleus, suprachiasmatic nucleus and ventromedial nucleus, whilst the supraoptic nucleus, paraventricular nucleus, arcuate nucleus and dorsomedial nucleus were devoid of labeling. Delta opioid labeling was sparse throughout most of the hypothalamus; however, moderate binding densities were detected in the suprachiasmatic and ventromedial nucleus. kappa Opioid labeling was also scant throughout the hypothalamus with the exception of the suprachiasmatic nucleus which was very densely labeled. Our results indicate that the 3 opioid receptors types are differentially distributed within the hypothalamus, although a significant overlap exists. In general, the distribution of hypothalamic opioid receptors correlates well with that of opioid-containing terminal fibers and may represent the anatomical substrate for opioid involvement in the hypothalamic regulation of autonomic, behavioral and neuroendocrine functions.  相似文献   

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