Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of repeated treatment of rats with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), 1.0 mg/kg, subcutaneously, twice daily for 7 days, on the stimulation of post- and presynaptic 5-HT1A receptors were examined. The postsynaptic responses, hypothermia and inhibition of the cage-leaving response, evoked by 0.05 mg/kg 8-OH-DPAT, were measured 48 hr after the final injection. Another postsynaptic response, the 5-HT syndrome (flat body posture and forepaw treading) was observed after the third injection of 8-OH-DPAT (1.0 mg/kg s.c.). One presynaptic response examined was the 8-OH-DPAT-induced decrease in the concentration of 5-hydroxyindoleacetic acid (5-HIAA), that indicates a decrease in turnover of 5-HT, due to stimulation of 5-HT receptors on the cell bodies and measured as the ratio of 5-HIAA to 5-HT in the hippocampus, hypothalamus and medulla oblongata. Another presynaptic response was the 8-OH-DPAT-induced decrease in the accumulation of 5-hydroxytryptophan (5-HTP) in the hippocampus and hypothalamus, after inhibition of L-aromatic amino acid decarboxylase by 3-hydroxybenzylhydrazine (NSD 1015), that is due to stimulation of autoreceptors on the 5-HT cell bodies. The kinetic properties of 5-HT1A receptors in the cerebral cortex and hippocampus, hippocampus alone, hypothalamus and medulla oblongata were determined with [3H]8-OH-DPAT. It was found that the postsynaptic effects were markedly attenuated after the treatment, the hypothermic effect already after a single dose.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Different effects on the responses of functional pre- and postsynaptic 5-HT1A receptors by repeated treatment of rats with the 5-HT1A receptor agonist 8-OH-DPAT. 169 32

Systemic administration of the neurotoxin 3-acetylpyridine (3-AP) to rats produced spontaneous episodes of spasmodic movement involving the trunk and limbs including torticollis, contortions of the trunk and rigid extension of the limbs. Because the neurotransmitter serotonin (5-HT) has been implicated in various human involuntary movement disorders, the functional and anatomical integrity of the 5-HT system in rats treated with 3-AP were examined. 5-HT-containing neurons in the brain stem were studied using immunohistochemical labeling with antiserum to 5-HT. Cells in the nucleus raphe obscurus were found to be altered following 3-AP treatment as shown by a decrease in 5-HT immunoreactivity as compared to control rats. No changes in 5-HT immunoreactivity were observed in any other region containing 5-HT cell bodies. Behaviorally, rats treated with 3-AP were 2.5-fold more sensitive to the ability of the 5-HT1A agonist 8-OH-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.33-3.3 mg/kg) to produce the 5-HT syndrome. Similarly, 3-AP-treated rats were 2-fold more sensitive to the selective 5-HT2 agonist 1-(2,5-dimethoxy-4-bromophenyl)-2-aminopropane (DOB; 0-1.0 mg/kg) at producing the head shake response. Although these behaviors associated with brain stem 5-HT receptors were potentiated by 3-AP, the hypothermic effect of 8-OH-DPAT which involves ascending mesencephalic 5-HT neurons was unchanged following 3-AP treatment. Treatment with 3-AP did not produce significant alterations of 5-HT or 5-hydroxyindoleacetic acid (5-HIAA) content in any brain region studied. Quantitative autoradiographic analysis of the density of 5-HT1A receptors labeled with [3H]8-OH-DPAT revealed that these sites were unchanged in regions of the brain (frontal cortex, hippocampus and brain stem) and in the spinal cord. Similarly, few changes in the density of 5-HT2 receptors measured with [3H]ketanserin were observed in various brain regions. These results suggest that neurons from the nucleus raphe obscurus are involved in the elicitation of 5-HT-mediated behavioral responses by 5-HT1A and 5-HT2 receptor agonists that are though to be mediated through brain stem and spinal cord mechanisms. In addition, because of the close neuroanatomical relationship of the nucleus raphe obscurus with various brain regions known to be involved in motor control, the destruction of this region by 3-AP may contribute to the spasmodic motor behaviors observed following 3-AP treatment.
 ...
PMID:Destruction of the nucleus raphe obscurus and potentiation of serotonin-mediated behaviors following administration of the neurotoxin 3-acetylpyridine. 169 5

The effects of 25 and 75 mg/kg p,p'-DDT on the CNS serotonergic system were examined in proestrous female rats. Females were treated with p,p'-DDT on the morning of proestrus and were sacrificed that evening. Levels of serotonin (5-HT) and its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA), were examined in cortex, hippocampus, hypothalamus and preoptic areas. The binding of 3'-8-OH-DPAT [2-hydroxy-2-N, N-(di-propylamino)-tetralin], an agonist for 5-HT1A receptors, was examined in hippocampus and frontal cortex. P,p'-DDT decreased the level of 5-HT in frontal cortex and hippocampus. Elevations in 5-HIAA were present in the hypothalamus but only at the higher dose of p,p'-DDT. The dose of 25 mg/kg p,p'-DDT produced an increase in the Bmax for 3H-8-OH-DPAT binding to frontal cortical and hippocampal membranes. Membrane preparations from females given 75 mg/kg p,p'-DDT fell into two categories. Some were similar to the control but with a slightly higher Kd; others could not be analyzed by traditional linear or nonlinear regression procedures because they showed a constant proportion of bound label, independent of the concentration of 3H-ligand in the reaction. In vitro, p,p'-DDT did not compete with 3H-8-OH-DPAT for binding to cortical membranes so it is unlikely that residual pesticide in the membrane preparation accounted for the binding results. These binding results are particularly interesting because, in previous studies, the dose of 25 mg/kg p,p'-DDT was shown to be more potent than 75 mg/kg p,p'-DDT in reducing female rodent lordosis behavior.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Serotonergic changes following proestrous treatment with p,p'-DDT. 170 93

The effects of 5-HT1A receptor agonists such as 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), BP-554 and buspirone on the serum corticosterone level were significantly more pronounced in female than in male mice. A similar sex difference was observed for the effect of 8-OH-DPAT on the plasma ACTH level. Pretreatment with proadifen, an inhibitor of microsomal drug-metabolizing enzymes, did not affect the sex difference in the effect of 8-OH-DPAT. The corticosterone response to 8-OH-DPAT in female mice was attenuated by ovariectomy. The effect of 8-OH-DPAT in ovariectomized mice was enhanced by chronic estradiol and the enhancement was blocked by testosterone. In male mice the corticosterone response to 8-OH-DPAT increased at 5 weeks after castration but had not changed at 2 weeks. Chronic estradiol enhanced the corticosterone response to 8-OH-DPAT in castrated mice. There was no difference between sexes in [3H]8-OH-DPAT binding to membranes and in the contents of 5-HT and 5-hydroxyindoleacetic acid in the hypothalamus. Accumulation of 5-hydroxytryptophan after decarboxylase inhibition in the hypothalamus was however greater in female than in male mice.
 ...
PMID:Gonadectomy changes the pituitary-adrenocortical response in mice to 5-HT1A receptor agonists. 183 34

Previous work in this laboratory demonstrated that the 19- and 35-day-old offspring of ethanol-fed rats have a significant deficiency of cortical serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), as well as a decrease in the number of total 5-HT1 receptors in the motor and somatosensory cortex. The present studies extend our previous reports by demonstrating that there is also a deficit of 5-HT and 5-HIAA in the motor cortex but not in the somatosensory cortex. In addition, we have shown that a deficit of 5-HT1A receptors in the motor and somatosensory cortices contributes to the deficit of total 5-HT1 receptors. In contrast, we did not observe any changes in the binding to 5-HT1B receptors in these cortical regions from the 19-day-old offspring of ethanol-fed rats. The present studies also examined the effects of in utero ethanol exposure on the early development of the serotonergic system. The results of these studies demonstrated a deficit of 5-HT and/or 5-HIAA in the brain stem as early as the 15th day of gestation (G15) and in the cortex as early as G19. In addition, we demonstrated a delay in both the normal developmental decline of 5-HT1A receptors in the brain stem and in the acquisition of cortical 5-HT1A receptors. No changes were found in the binding of [125I]cyanopindolol to 5-HT1B receptors in either region of fetal or neonatal rats exposed to ethanol in utero.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effects of in utero ethanol exposure on the developing serotonergic system. 192 43

Ipsapirone, a new anxiolytic drug with a high affinity to 5-HT1A receptors, given in a dose of 10 mg/kg ip markedly accelerated noradrenaline disappearance after inhibition of tyrosine hydroxylase with alpha-methyl-p-tyrosine (250 mg/kg ip) in the cortex, hippocampus and hypothalamus of male Wistar rats. It also increased disappearance of dopamine and the level of 3,4-dihydroxyphenylacetic acid and homovanillic acid in the striatum. At the same time, the level of 5-hydroxyindoleacetic acid was decreased in the cortex, striatum, hypothalamus, but not changed in the hippocampus. 8-OH-DPAT, a selective agonist of 5-HT1A receptors, used in a dose of 5 mg/kg sc was less effective, having accelerated noradrenaline disappearance in the cortex and hypothalamus, and having increased only the level of homovanillic acid in the striatum. The effect of ipsapirone on catecholamine turnover might be secondary in relation to inhibition of the serotonin neurons. A direct interaction between ipsapirone and its metabolite 1-PP with alpha 1- and alpha 2-adrenoceptors is very likely, too.
 ...
PMID:Ipsapirone, a new anxiolytic drug, stimulates catecholamine turnover in various regions of the rat brain. 198 Mar 61

1-(m-Trifluoromethylphenyl)-4-(p-aminophenylethyl)piperazine (LY 156163), reported previously to have selective affinity for the 5-HT1A subtype of serotonin receptor in vitro, was studied at doses of 1.25 to 20 mg/kg i.p. in rats to determine if it had properties characteristic of centrally acting serotonin agonists. LY 165163 decreased whole brain concentrations of the serotonin metabolite, 5-hydroxyindoleacetic acid, but not of serotonin itself, decreased the rate of accumulation of 5-hydroxyindoleacetic acid after probenecid administration to block its efflux from brain, decreased the rate of decline in serotonin concentration after inhibition of serotonin synthesis with alpha-propyldopacetamide and decreased the accumulation of 5-hydroxytryptophan after decarboxylase inhibition by m-hydroxybenzylhydrazine. LY 165163 also decreased 5-hydroxyindoleacetic acid concentrations in two specific brain regions, striatum and hypothalamus. Serum concentrations of corticosterone and prolactin were increased by doses of LY 165163 that reduced serotonin turnover. These effects are all consistent with evidence from other studies that LY 165163 is a centrally acting serotonin agonist. LY 165163 also increased the concentrations of two dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, measured in whole brain as well as in striatum and hypothalamus, but did not alter dopamine concentration. The accumulation of dopa after decarboxylase inhibition was accelerated by LY 165163. The increases in hormone concentrations in serum and of dopamine metabolite concentrations in brain were not antagonized by pretreatment with metergoline, a serotonin antagonist. The mechanisms of those effects require further study.
 ...
PMID:Central serotonin agonist actions of LY 165163, 1-(m-trifluoromethylphenyl)-4-(p-aminophenylethyl) piperazine, in rats. 243 93

The 5-hydroxytryptamine1A-receptor agonist 8-hydroxy-2-(n-dipropylamino) tetralin (8-OH-DPAT, 0.1 mg kg-1 i.v.) decreased the height of the extracellular 5-hydroxyindoleacetic acid (5-HIAA) oxidation peak recorded in the suprachiasmatic nucleus (SCN) of the anaesthetized rat by use of differential pulse voltammetry. The decrease in extracellular 5-HIAA produced by 8-OH-DPAT could be partially attenuated by prior administration of the non-selective 5-HT receptor antagonist methiothepin (1 mg kg-1 i.v.). The 5-HT2-receptor antagonist ritanserin (0.2 mg kg-1 i.v.) did not appear to block the effects of 8-OH-DPAT. The selective ligand for 5-HT1A recognition sites TVX Q 7821 (isapirone, 1 mg kg-1 i.v.) decreased the extracellular level of 5-HIAA in the SCN but to a lesser extent than 8-OH-DPAT. The response to 8-OH-DPAT was attenuated by prior administration of TVX Q 7821 to a level suggesting that TVX Q 7821 had blocked the effect of intravenous 8-OH-DPAT. Idazoxan (0.2 mg kg-1 i.v.) an alpha 2-adrenoceptor antagonist, completely blocked the effect of 8-OH-DPAT on the 5-HIAA oxidation peak recorded in the SCN, whilst having no effect on the 5-HIAA oxidation peak when given alone. At a dose of 0.5 mg kg-1 i.v. idazoxan induced a 120% increase in the height of the indole oxidation peak, suggesting that 5-HT release and metabolism in the rat SCN may be influenced by tonic adrenergic inputs. The data in this paper suggest that 5-HT1A- and alpha 2-receptors are involved in the effects of i.v. administered 8-OH-DPAT on 5-HT release and metabolism in the SCN in vivo.
 ...
PMID:Involvement of 5-HT1A- and alpha 2-receptors in the decreased 5-hydroxytryptamine release and metabolism in rat suprachiasmatic nucleus after intravenous 8-hydroxy-2-(n-dipropylamino) tetralin. 243 Jun 56

The present study was undertaken to investigate the hyperphagic responses to the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), in young and adult rats fed either a powder diet or pellets. In the young rats, 8-OH-DPAT (500 micrograms/kg s.c.) increased the consumption of pellets--but not powder--during the 2 h following drug administration. On the other hand, 8-OH-DPAT did not promote hyperphagia in adult rats presented with either pellets or a powdered diet. The influence of the 5-HT1A agonist on midbrain serotonin (5-hydroxytryptamine, 5-HT) turnover was examined. Administration of 8-OH-DPAT (500 micrograms/kg s.c.) induced similar decreases in 5-HT turnover, as reflected by the ratio of 5-hydroxyindoleacetic acid (5-HIAA) to 5-HT, in young and adult rats 1 h after administration. Nevertheless, some metabolic responses to 8-OH-DPAT were found to be influenced by age. Young and adult rats were injected with a low dose of 8-OH-DPAT (50 micrograms/kg s.c.) to specifically test the presynaptic regulation of 5-HT turnover. Again, midbrain 5-HIAA to 5-HT ratios were decreased to the same extent in both young and adult rats. The results suggest that (i) gnawing may be an important parameter in the food consumption that is triggered by a high dose of 8-OH-DPAT, (ii) analysis of the presynaptic effects of 8-OH-DPAT on 5-HT turnover cannot solely explain the influence of the agonist on feeding behavior.
 ...
PMID:Feeding responses to a high dose of 8-OH-DPAT in young and adult rats: influence of food texture. 245 45

This study concentrates on the role of the serotonin system in mediating the proestrous effects of chlordecone on female rodent sexual behavior. The pesticide was examined within the context of serotonin changes taking place on proestrous. Between morning and evening on the day of proestrus there was an increase in 3H-5-HT binding, an increase in serotonin (5-HT) and an increase in 5-hydroxyindoleacetic acid (5-HIAA). Proestrous treatment with chlordecone attenuated the increase in 5-HT and in 3H-5-HT binding but had no effect on 5-HIAA. These findings suggest that the pesticide blocked proestrous changes essential for the female's development of sexual receptivity. The 5-HT1A agonist, 8-OH-DPAT, was an inefficient competitor for 3H-5-HT binding in frontal cortex of females treated with chlordecone. It is speculated that the pesticide disrupts a balance between serotonin sites which facilitate and those which inhibit sexual behavior. Consistent with this speculation, the 5-HT agonist, quipazine, partially attenuated chlordecone's reduction of sexual behavior. Finally, the rapid effects of estradiol and chlordecone on 3H-5-HT binding sites were compared in ovariectomized female rats. These results showed no resemblance between the effects of chlordecone and those of estradiol.
 ...
PMID:Proestrous effects of chlordecone on the serotonin system. 246 47


<< Previous 1 2 3 4 5 6 7 8 Next >>