1,722,301 research outputs found
Catalepsy induced by SCH 23390 in rats.
No full textThe ability of SCH 23390 as compared to haloperidol to produce catalepsy in rats was evaluated in three tests for catalepsy. SCH 23390 produced catalepsy in all three tests with ED50 (mg/kg s.c.) of 0.017 on the vertical grid, 0.023 on the horizontal bar and 0.038 on the 'four corks'. Haloperidol produced catalepsy with ED50 (mg/kg s.c.) of 0.048 on the vertical grid, 0.042 on the horizontal bar and 0.065 on the four corks. Catalepsy by SCH 23390 and by haloperidol was prevented by scopolamine and potentiated by alpha-methyl-p-tyrosine pretreatment. Catalepsy induced by SCH 23390 was also prevented by specific D-2 receptor agonists such as pergolide, lisuride and bromocriptine but not by the D-1 receptor agonist SKF 38393. The results demonstrate that SCH 23390 is potently cataleptogenic and that the catalepsy it produces has a pharmacologic profile typical of that produced by potent and specific D-2 antagonists
SCH 23390 antagonizes apomorphine- and ergot-induced hypothermia.
No full textThe reportedly specific D-1 dopamine (DA) receptor antagonist SCH 23390 significantly reduced the hypothermia elicited by various DA receptor agonists like apomorphine, pergolide and lisuride. When tested against equihypothermic doses of each agonist, SCH 23390 significantly reduced the hypothermia elicited by apomorphine (0.2 mg/kg s.c.) and by pergolide (0.1 mg/kg i.p.) at doses of 0.025 mg/kg s.c. Doses of 0.050 mg/kg s.c. of SCH 23390 were necessary to reduce the hypothermia elicited by 0.012 mg/kg s.c. of lisuride. Pretreatment with the specific D-2 antagonist (-)sulpiride (50 mg/kg i.p.) completely prevented the hypothermia elicited by lisuride (0.012 mg/kg i.p.), pergolide (0.1 mg/kg i.p.) and apomorphine (0.2 mg/kg s.c.) and shifted to the right the dose-response curve for agonist-induced hypothermia. A study of the interaction between 0.05 mg/kg s.c. of SCH 23390 with various doses of the agonists showed that the effectiveness of SCH 23390 in antagonizing the hypothermia was maximal towards apomorphine and least towards lisuride for which significant antagonism was observed only against the lowest dose tested (0.012 mg/kg s.c.). The reportedly specific D-1 receptor agonist SKF 38393 given in doses up to 20 mg/kg i.p. or intracerebroventricularly up to 100 micrograms failed to influence body temperature while it evoked intense grooming and stimulated motility
The synchronization index and RF changes measured during SCH-23390 application.
No full text<p>A: The comparison of synchronization index in early- and late-adaptation during control (open triangles) and SCH application (filled triangles). SCH = SCH-23390. B: Bar plots showing mean synchronization index for control and SCH-23390 respectively (mean ± S.E., paired t-test, *, p<0.05). (E) = early-adaptation; (L) = late-adaptation. C: The comparison of RF in early- and late-adaptation for control (open circles), SCH-23390 (filled circles). D: Bar plots showing mean RF area for control and SCH-23390 respectively (mean ± S.E., paired t-test, *, p<0.05).</p
Absence of [3H]SCH 23390 specific binding sites in anterior pituitary: Dissociation from effects on prolactin secretion
No full textWe extended a previous study that had shown the selective D1 receptor antagonist SCH 23390, at relatively high doses, to stimulate prolactin (PRL) secretion in the rat and weakly inhibit [3H]spiperone binding to striatum and anterior pituitary (AP) membranes. No specific [3H]SCH 23390 binding sites, up to the micromolar range, were detected in rat AP while specific, saturable [3H]SCH 23390 binding sites (low nanomolar range) were observed in the striatum. In vivo SCH 23390 (1 mg/kg s.c.) induced higher plasma PRL levels, not reversible by the D1 agonist SKF 38393. Similarly the postsynaptic serotonin (5-HT) antagonists metergoline and cyproheptadine did not influence the SCH 23390 effect on PRL. SCH 23390 was also unable to antagonize the decrease of PRL secretion induced by the selective D2 agonist LY 171555. However this latter compound prevented SCH 23390 as well as sulpiride from increasing the PRL concentrations above the control values. These data rule out the possibility that D1 or 5-HT receptors mediate the stimulation of PRL release by SCH 23390. This effect is more likely to be due to weak indirect interaction with AP-D2 receptors, as indicated by the non-competitive inhibition of [3H]spiperone binding to AP exerted by SCH 23390. Alternatively, non-specific mechanism triggered by the multiple behavioral changes elicited by such high doses of SCH 23390 may be involved. © 1987
Chronic imipramine reduces [3H]SCH 23390 binding and DA-sensitive adenylate cyclase in the limbic system
No full text[3H]SCH 23390 binding and dopamine (DA)-stimulated adenylate cyclase activity were measured in brain membrane preparations from rats chronically treated with imipramine (10 mg/kg twice daily for 14 days). [3H]SCH 23390 binding sites were decreased by 27% in the limbic system but only 14% in the striatum. The responsiveness of adenylate cyclase to DA was reduced by 38% in the limbic system but was not modified in the striatum. Concomitant treatment with alpha-methyltyrosine (alpha-MPT) (50 mg/kg daily for 14 days) prevented the imipramine-induced reduction in both [3H]SCH 23390 binding sites and the responsiveness of adenylate cyclase to DA
Sedation and sleep induced by high doses of apomorphine after blockade of D-1 receptors by SCH 23390
No full textThe effect of SCH 23390, a selective blocker of D-1 receptors, on apomorphine-induced behavioural and EEG changes was studied in rats. In control rats, a low dose of apomorphine (50 micrograms/kg s.c.) produced sedation associated with EEG synchronization. A high dose of apomorphine (1 mg/kg s.c.) produced stereotypy associated with EEG desynchronization. At the dose of 1 mg/kg i.p., SCH 23390 decreased motor activity but failed to alter the EEG pattern. The administration of either the low or high dose of apomorphine to SCH 23390-treated rats elicited a marked sedative response associated with EEG synchronization. The EEG synchronization produced by apomorphine (50 micrograms/kg) in SCH 23390-treated rats was prevented by (-)-sulpiride (25 mg/kg i.p.), a D-2 receptor blocker. It is concluded that by preventing the excitatory response to apomorphine SCH 23390 discloses the existence of a population of D-2 receptors mediating sedation and sleep
SCH-23390 antagonism of a D-2 dopamine agonist depends upon catecholaminergic neurons
Get PDFSCH-23390, a selective D-1 dopamine antagonist, was found to antagonize the locomotor stimulation induced by LY-171555, an action similar to that for haloperidol in control animals. However, this action of SCH-23390 was prevented in rats treated with 6-hydroxydopamine (6-OHDA) or with reserpine plus α-methyl-tyrosine pretreatment. These results indicate that the action of SCH-23390 to antagonize D-2 dopamine receptor actions is dependent upon functional catecholamine-containing neurons. In contrast to the lack of action of SCH-23390 to antagonize LY-171555 in 6-OHDA-treated rats, SCH-23390 blocked the locomotor stimulation induced by SKF-39393, a D-1 dopamine agonist, after this treatment. Thus, D-1 dopamine receptors are distinct from D-2 receptor sites and can exhibit a behavior similar to that observed when D-2 receptors are stimulated. These data suggest that D-1 receptor sites modulate D-2 dopamine receptor function through a mechanism dependent upon functionally intact catecholamine-containing neurons
D1 dopamine receptors in the rat retina: effect of dark adaptation and chronic blockade by SCH 23390
No full textChronic administration of SCH 23390 (0.03 mg/kg s.c., three times daily), a selective D1 dopamine (DA) receptor blocker, markedly increased the [3H]SCH 23390 binding in the rat retina. As revealed by the Scatchard plot analysis of saturation data from retinal homogenates, chronic SCH 23390 increased the total number of binding sites by 34% when compared to tissue from solvent-treated rats but failed to change the apparent affinity of [3H]SCH 23390 for its binding sites. The up-regulation of [3H]SCH 23390 binding sites was paralleled by an increase in the sensitivity of retina DA-sensitive adenylate cyclase. In fact, DA (5 X 10(-6) M to 10(-4) M) produced a higher accumulation of cyclic AMP (from 58 to 128%) in the retina of SCH 23390-treated rats as compared to the accumulation (from 35 to 80%) found in tissue from solvent-treated rats. Since dark adaptation decreases dopaminergic function in the rat retina, the influence of environmental lighting on [3H]SCH 23390 binding and DA-sensitive adenylate cyclase activity was studied. After 4 h of dark adaptation the density of [3H]SCH 23390 binding sites was higher (32%) than that from light-adapted rats. On the other hand, dark adaptation failed to change the apparent affinity of [3H]SCH 23390 for its binding sites. Moreover, DA elicited a greater stimulation of adenylate cyclase activity in homogenates of retina from dark-adapted rats. Thus, the maximum adenylate cyclase response to DA resulted higher in the retina of dark-adapted rats (152%) than that found in the retina of light-adapted animals (97%).(ABSTRACT TRUNCATED AT 250 WORDS
Stimulation of forward locomotion by SCH-23390 and raclopride in d-amphetamine-treated rats
No full textIn d-amphetamine-treated (4.0 mg kg(-1) s.c.) rats the selective dopamine D1 and D2/3 receptor antagonists SCH-23390 (2.5-20.0 microg kg(-1) s.c.) and raclopride (12.5-100.0 microg kg(-1) s.c.), respectively, produced a biphasic pattern of effects on forward locomotion, as observed in an open-field arena (approximately 0.5 m2). Thus, at the low doses of SCH-23390 (2.5-10.0 microg kg(-1)) or raclopride (12.5-50.0 microg kg(-1)), there was a statistically significant increase in forward locomotion, followed by suppression of the behavior at the higher doses. The SCH-23390-induced (5.0 microg kg(-1)) stimulation of forward locomotion was partially antagonized by concomitant raclopride treatment (12.5-25.0 microg kg(-1)) and the corresponding raclopride-induced (12.5 microg kg(-1)) stimulation was fully antagonized by treatment with SCH-23390 (2.5-5.0 microg kg(-1)). Furthermore, the SCH-23390- or raclopride-induced stimulation of forward locomotion was also antagonized by treatment with the alpha1-adrenoceptor antagonist prazosin (1.0 mg kg(-1) s.c.). These observations suggest that under conditions of an increased general tone at brain dopamine receptors, there is a mutual inhibitory synergy between dopamine D1 and D2/3 receptors
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