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H Coirini

Publications and source records attributed to H Coirini.

At least 19 recordsLinked to original sources
PubMed1999

Site-specific effects of the nonsteroidal anti-inflammatory drug lysine clonixinate on rat brain opioid receptors.

In addition to effects in the periphery through inhibition of prostaglandin synthesis, several lines of evidence suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) act in the central nervous system. The possibility that the central action of NSAIDs involves regulation of opioid receptors was investigated by quantitative autoradiography of mu, delta, and kappa sites in rat brain slices. Increased (p < 0.05) labeling of mu receptors was observed in thalamic nuclei, gyrus dentate, and layers of the parietal cortex of rats treated for 10 days with lysine clonixinate. Labeling of delta receptors was lower in the lateral septum, and kappa sites decreased in thalamic nuclei. These effects were not mediated through direct interaction with opioid-binding sites, since receptor-binding assays using rat brain membranes confirmed that clonixinate up to 1 x 10(-4) mol/l does not inhibit mu, delta, and kappa receptor specific binding. Central effects of NSAIDs might, therefore, involve interaction with the opioid receptor system through indirect mechanisms.

Analgesics↗
PubMed1998

Differential modulation of dopamine D1-receptor binding and mRNA expression in the basal ganglia by the D1-receptor antagonist, SCH-23390.

Dopamine D1-receptor binding in the basal ganglia is differentially regulated by subtype nonspecific dopamine antagonists such as the antipsychotic, Fluphenazine. The purpose of the present study was to determine the relative contributions of D1 and D2 receptor systems in the regulation of basal ganglia D1-receptor binding. Rats were injected twice daily for 21 days with saline, the D1-receptor antagonist, SCH-23390, the D2-receptor antagonist, Raclopride, or both SCH-23390 and Raclopride. Dopamine D1-receptor levels (as indicated by [125I]SCH-23982 binding) and mRNA expression were measured using receptor autoradiographic and in situ hybridization histochemical techniques. [125I]NCQ-298 binding to D2-receptors was also measured as a positive control for the effects of Raclopride. SCH-23390 administration independently increased [125I]SCH-23982 binding in a region-dependent manner with the greatest increases occurring in the entopeduncular nucleus. SCH-23390 also increased D1-receptor mRNA expression in specific striatal subregions suggesting that increases in binding were related to changes in receptor synthesis. In addition, Raclopride independently enhanced D2 binding with comparable increases observed in extrastriatal regions and increases of a lesser magnitude in the striatum. These data show that the modulation of basal ganglia D1-receptor binding observed in animals treated with nonselective antagonists is due primarily to the blockade of D1-receptors. The differential enhancement in basal ganglia D1 binding observed after D1-receptor blockade may be due to anatomical or phenotypic heterogeneity within the population of striatal D1-receptor synthesizing neurons. Similarly, the differential enhancement in striatal and extrastriatal D2-receptor binding may be due to differences in the regulation of striatal and extrastriatal D2-receptor synthesizing neurons.

Animals↗
PubMed1997

Modulation of basal ganglia neurotransmission by the classical antipsychotic fluphenazine is due in part to the blockade of dopamine D1-receptors.

Classical antipsychotics, such as fluphenazine, influence neurotransmission by blocking both dopamine D1- and D2-receptors which in turn results in widespread adaptive changes in the neurochemistry of the basal ganglia. The purpose of the present study was to determine the role of D1-receptors in mediating some of these neurochemical events, including changes in D1- and D2-receptor binding, and the expression of preproenkephalin and glutamic acid decarboxylase mRNAs. For these experiments, rats were given a depot injection of fluphenazine decanoate or injected twice daily for 21 days with the D1-receptor antagonist SCH-23390. An additional group received both fluphenazine and SCH-23390 and controls were given saline. Fluphenazine administration decreased D2-receptor binding throughout the basal ganglia while SCH-23390 was without effect. In contrast to the uniform reduction in D2-receptor binding, fluphenazine altered D1-receptor binding in a region-dependent manner. Region-dependent changes were also observed in animals given SCH-23390 which increased binding in the entopeduncular nucleus and posterior caudate-putamen without affecting other brain regions. Both fluphenazine and SCH-23390 significantly enhanced preproenkephalin and glutamic acid decarboxylase (GAD) mRNA expression in the anterior striatum. Fluphenazine also increased GAD mRNA levels in the entopeduncular nucleus. Together, these results indicate that the attenuation of D1-receptor-mediated neurotransmission modulates a number of clinically relevant neurochemical processes in the basal ganglia.

Analysis of Variance↗
PubMed1995

Neuroleptics differentially modulate central dopamine D1-receptor binding.

The effect of the classical neuroleptic, fluphenazine, on dopamine D1-receptor binding was examined in different regions of the basal ganglia. Whereas exposure to fluphenazine for 18 months reduced [125I]SCH-23982 binding to D1-receptors in the caudate putamen, nucleus accumbens and olfactory tubercle, binding in the entopeduncular nucleus was enhanced after fluphenazine treatment. Competition studies indicated that the region-dependent changes in [125I]SCH-23982 binding after fluphenazine exposure were not due to differences in the affinity of fluphenazine or other dopamine ligands for D1-binding sites. These data suggest that in addition to modulating striatal function, classical neuroleptics may also alter neurotransmission in the basal ganglia by enhancing dopamine receptor binding in the entopeduncular nucleus.

Animals↗
PubMed1995

Time-dependent effects of dexamethasone on glutamate binding, ornithine decarboxylase activity and polyamine levels in the transected spinal cord.

Evidence exists that the spinal cord is a glucocorticoid-responsive tissue, and glucocorticoids have beneficial effects in cases of spinal cord injury. Using sham-operated rats, spinal cord transected (TRX) rats, and TRX animals receiving dexamethasone (DEX) 5 min or 24 h post-lesion, we have examined the following GC-sensitive parameters 6 h after DEX treatment: (1) binding of glutamate to NMDA-sensitive receptors; (2) the activity of ornithine decarboxylase (ODC); and (3) levels of polyamines. We found that glutamate binding in the dorsal horn (Laminae 1-2) and central canal were upregulated in TRX rats, whereas DEX had an additional stimulatory effect. 24 h post-lesion, glutamate binding was unmodified in TRX or TRX+DEX rats. ODC activity was increased 10-fold in rats killed on the day of transection but only 2-fold 24 h post-lesion. DEX reduced ODC activity on transection day but highly increased it when given 24 h after surgery. The content of the polyamines spermidine and spermine were unchanged after TRX or DEX treatment, in contrast to putrescine which increased in TRX rats and further increased in TRX+DEX rats when measured the day post-lesion. Thus, parallel increases in ODC and putrescine 1 day after the lesion, suggest that glucocorticoid effects on growth responses due to polyamines may develop at a late period. The changes of glutamate binding in the dorsal horn and central canal due to early glucocorticoid treatment, further suggest hormonal modulation of neurotransmission in sensitive areas of the deafferented spinal cord.

Animals↗
PubMed1994

Characterization of dopamine receptor binding sites in the subthalamic nucleus.

Experiments were undertaken to determine the distribution and binding profile of dopamine (DA) receptors within a key extra-striatal region of the rat basal ganglia, the subthalamic nucleus (STh). Analysis of [125I]NCQ-298 autoradiograms showed that binding sites of the D2-receptor family are abundant in the STh. Competition studies indicated that these sites were specifically of the D2 subtype. However, contrary to previously published data, [125I]SCH-23982 autoradiograms failed to reveal D1 receptor binding in the STh. These data suggest that DA acting at D2 receptors may directly modulate STh neural activity and furthermore that the antagonism of STh D2 receptor binding by neuroleptics may be involved in the expression of extrapyramidal motor disturbances.

Animals↗
PubMed1994

Binding of the anti-inflammatory steroid deflazacort to glucocorticoid receptors in brain and peripheral tissues. In vivo and in vitro studies.

Deflazacort (DFC) is a heterocyclic glucocorticoid with anti-inflammatory activity but with decreased side effects. In this study, we have evaluated the capacity of DFC and other glucocorticoids to reach the central nervous system (CNS) in vivo by measuring changes of [3H]dexamethasone (DEX) binding to glucocorticoid receptors (GR) in vitro. GR occupation was effected by DEX in the cerebral cortex, hippocampus, pituitary, liver and thymus, with DFC showing a similar profile except for the cerebral cortex. In contrast, corticosterone weakly occupied GR in the thymus, pituitary and hippocampus and methyl-prednisolone was active only in peripheral tissues. Furthermore, IC50 for DEX in vitro amounted to 15-17 nM in the hippocampus and liver, whereas IC50 for the active metabolite 21-deacetyl-DFC (21-OH-DFC) was 4 times higher. 21-OH-DFC bound to type II and was absent from type I GR. When tested in equipotent doses based on IC50 analysis, DFC and DEX similarly induced in vivo ornithine decarboxylase activity in hippocampus and liver, although body weight loss after chronic treatment was significantly less for DFC. The results show that DFC distributes on the CNS similarly to DEX, induces ornithine decarboxylase activity but presents less intensive catabolic effects, making it suitable for use as an anti-inflammatory steroid during chronic therapeutic regimes.

Animals↗
PubMed1992

Regulation of flunitrazepam binding in the dorsal horn of the spinal cord by adrenalectomy and corticosteroids.

Adrenal corticosteroids and adrenalectomy (ADX) have opposing effects on benzodiazepine binding sites in brain regions. These treatments were employed to study [3H]flunitrazepam (FLU) binding in regions punched out from the rat spinal cord. We found that binding was higher in dorsal horn than in ventral horn, and minimal in white matter. Clonazepam and RO 15-1788 largely displaced [3H]FLU binding, whereas RO 5-4864 was weakly active. Four days post-ADX, binding increased exclusively in the dorsal horn, and this effect was reversed by administration of corticosterone (CORT), but not dexamethasone (DEX) or aldosterone (ALDO) given over 4 days. When endogenous CORT was increased by administration of cold stress to adrenal-intact rats, reduced benzodiazepine (BDZ) binding was also observed in the dorsal horn. When added in vitro, only ALDO and not CORT or DEX, inhibited [3H]FLU binding. It is suggested that steroids with affinity for the type I corticosteroid receptor (CORT, ALDO) decrease [3H]FLU binding to a neural-type BDZ receptor in the dorsal horn. Reduction of the inhibitory BDZ system may be physiologically important, and can partly explain the enhancement of excitatory synaptic transmission produced by corticosteroids at the level of the spinal cord.

Adrenal Glands↗
PubMed1992

Sex differences in the regulation of oxytocin receptors by ovarian steroids in the ventromedial hypothalamus of the rat.

The facilitation of sexual receptivity by oxytocin (OT) in female rats is related to the regulation of oxytocin receptors (OTR) by ovarian steroids in the ventromedial nuclei (VMN) of the hypothalamus. In a previous study, we have shown that estradiol benzoate (EB) causes a twofold increase in OTR binding in the VMN. Progesterone (P) then modulates levels of the estrogen-induced OTR and increases the area occupied by the receptors by acting on the neuronal membrane. In the present study, we compared the effects of EB and P on OTR binding between males and females. In both sexes, EB increased the density of OTR and the area covered by the receptors at the level of the medial and caudal VMN. In estrogen-primed females, P further increased OTR levels in the medial VMN and the area covered by OTR at the level of the caudal VMN. By contrast, P did not modulate OTR binding in estrogen-primed males. Thus, the behavioral insensitivity of male rats to ovarian hormones, in particular to P, may be related to sex differences affecting the modulation of OTR binding.

Animals↗
PubMed1991

Binding of [3H]cholecystokinin in the ventromedial hypothalamus is modulated by an afferent brainstem projection but not by ovarian steroids.

The ventromedial nuclei (VMN) of the hypothalamus are innervated by cholecystokinin-immunoreactive (CCK-IR) fibers originating in the dorsal parabrachial nuclei (PBS). They also contain high levels of receptors for CCK and binding of [125I]CCK to these receptors is modulated by estrogen. In the present study, we show that unilateral lesion of the PBS increases the binding of the sulphated octapeptide of [3H]cholecystokinin ([3H]CCK) within the ipsilateral VMN of the hypothalamus, but not within other brain nuclei that contain receptors for CCK. Thus, CCK fibers originating in the PBS selectively innervate the VMN and CCK receptors within the VMN are postsynaptic to parabrachial afferents. However, treatment of ovariectomized rats with estradiol benzoate and progesterone did not affect the binding of [3H]CCK in the VMN, even after lesion of the parabrachial afferents.

Animals↗
PubMed1991

Ovarian steroid modulation of [3H]muscimol binding in the spinal cord of the rat.

[3H]Muscimol binding was measured in the lumbar spinal cord of female rats by in vitro quantitative autoradiography. Ovariectomized rats were treated subcutaneously with either oil, estradiol benzoate (EB) or EB plus progesterone (P) in a regime known to reliably induce sexual receptivity. The level of [3H]muscimol binding was highest in laminae I-III and in the region around the central canal. Binding was lower in laminae IV-VI and was frequently undetectable in the ventral horn. There was a significant increase in the level of binding in laminae I-III after EB treatment. There was also a significant increase after treatment with EB+P in comparison to both the ovariectomized and EB-treated groups in this same region of the spinal cord.

Animals↗
PubMed1991

Regulation by dopaminergic neurotransmission of dopamine D2 mRNA and receptor levels in the striatum and nucleus accumbens of the rat.

The effect of dopamine depletion or pharmacological blockade of dopamine receptors on striatal and accumbens dopamine D2 mRNA and receptor levels was assessed by in situ hybridization histochemistry and receptor autoradiography. The time course of pharmacological blockade with haloperidol demonstrates a complex mode of regulation of dopamine D2 mRNA and receptor levels. By day 8 of haloperidol treatment, D2 mRNA and receptor levels were decreased (up to 20%) in the medial and anterior aspects of the caudate-putamen (mCPU and aCPU) and the nucleus accumbens (NAc). However, by day 21 of haloperidol treatment, D2 mRNA and receptor were increased relative to vehicle-injected controls. Likewise, unilateral dopamine depletion due to 6-hydroxydopamine (6-OHDA) lesions of mesencephalic dopaminergic neurons resulted in decreased levels of D2 receptor mRNA by day 8 post-lesion in the ipsilateral mCPU, aCPU and the NAc. However, at days 14 or 21 post-lesion, there was a reversal of the effect with increases of up to 22% in all brain regions ipsilateral to the lesion. Although no decreases in receptor level were observed at day 8, significant increases in receptor level in all three brain regions were detected at days 14 and 21 post-lesion. The results demonstrate that midbrain dopaminergic innervation exerts tonic effects on the levels of dopamine D2 receptor and mRNA in the caudate-putamen and the nucleus accumbens of the rat. Changes in receptor level are frequently accompanied by comparable changes in mRNA level, indicating a mass action relationship between receptor level and receptor biosynthesis in these forebrain regions in the rat.

Animals↗
PubMed1991

Steroid hormones as mediators of neural plasticity.

Steroid and thyroid hormone receptors are expressed in the developing brain and persist throughout adult life. They mediate a variety of effects on the brain, ranging from developmental effects of thyroid hormone and the process of sexual differentiation to the cyclic changes during reproductive cycles in adult female animals. This review summarizes data from the author's laboratory on three topics: (1) actions of extradiol and progesterone on the ventromedial nucleus of the hypothalamus in adult female and male rats, showing both the cyclicity and the consequences of brain sexual differentiation; (2) actions of estradiol on the cholinergic neurons of the basal forebrain of the female and male rat, reflecting the plasticity of the adult cholinergic system as well as sex differences which are developmentally programmed; and (3) diverse actions of estrogens, thyroid hormone and glucocorticoids on the morphology of hippocampal neurons. The review concludes by discussing the interactions between "organizational" (i.e. developmental) effects and the "activational" effects of steroids on the mature nervous system in relation to the environmental control of brain gene expression.

Animals↗
PubMed1991

Light-dark differences in behavioral sensitivity to oxytocin.

Ovariectomized female rats treated with estradiol benzoate (EB) and progesterone (P) were infused intracerebroventricularly with a low (200 ng) or high (1 microgram) dose of oxytocin (OT). The low dose of OT facilitated lordosis behavior only during the dark phase of the light-dark cycle in females that were pretreated with low doses of EB (2 micrograms) and P (250 micrograms). In contrast, the high dose of OT facilitated lordosis behavior during both the light and the dark phases but only in long-term ovariectomized females that were primed with large amounts of EB (2 x 10 micrograms) and P (500 micrograms). In females that were primed with lower amounts of ovarian steroids, the high dose of OT failed to increase levels of lordosis responding in either the dark or light phase. Thus, when female rats are treated with physiological amounts of ovarian hormones and OT, they are more sensitive to the facilitative effects of the OT on lordosis behavior during the dark phase.

Animals↗
PubMed1991

The regulation of oxytocin receptor binding in the ventromedial hypothalamic nucleus by testosterone and its metabolites.

Oxytocin (OT) receptor binding in the ventromedial hypothalamic nucleus is regulated by testosterone (T) in male rats. However, T is metabolized in the brain, and many of the central effects of T are mediated by its metabolites. The experiments reported here were designed to determine whether T affects OT receptor binding directly or through the action of its metabolites 17 beta-estradiol and 5 alpha-dihydrotestosterone. Adult male rats were either sham operated or castrated and treated 1 week later with T propionate (TP), 17 beta-estradiol benzoate (EB), dihydrotestosterone benzoate (DHTB), DHTB plus EB, or oil. OT receptor binding was assessed autoradiographically using [125I]d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)]OVT. In addition, seminal vesicle weights were measured as an index of androgenic activity. These experiments showed that TP and DHTB plus EB increased OT receptor binding in the ventromedial hypothalamic nucleus to the levels in intact males. Treatment with EB alone partially reinstated binding to the levels in intact males, while DHTB treatment was without effect. Castrated males treated with either TP or DHTB had seminal vesicle weights comparable to those of gonadally intact males and greater than those of animals in all other steroid conditions, indicating that sufficient levels of circulating steroids were attained in these groups. These data suggest that the induction of hypothalamic OT receptor binding by T is the result of the combined actions of estradiol and dihydrotestosterone. However, the mechanism underlying this interaction is unknown.

Animals↗