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)

Cerebrospinal fluid (CSF), collected repeatedly from White Carneau pigeons chronically implanted with guide cannulae located in the lateral ventricles, was analyzed for metabolites of serotonin, dopamine and norepinephrine after acute and chronic administration of buspirone or 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Following the acute administration of 3.0 mg/kg buspirone, levels of 5-hydroxyindoleacetic acid (5-HIAA) decreased, while increases occurred in the dopamine metabolites homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC). Decreases in 5-HIAA persisted throughout the chronic dosing regimen (36 days), while dopamine metabolites returned to control levels within 8 days. When chronic buspirone was discontinued, levels of 5-HIAA were restored to predrug control levels, while levels of HVA, DOPAC and 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) decreased. All metabolites returned to predrug control levels within one week following buspirone discontinuation except for MHPG, which remained depressed. When the acute effects of buspirone were reexamined, levels of 5-HIAA were again significantly decreased, while HVA and DOPAC levels, as well as those of MHPG, increased significantly. Acute administration of the 5-HT1A receptor ligand 8-OH-DPAT (3.0 mg/kg) resulted in large decreases in 5-HIAA levels that persisted throughout the period of chronic administration. Neither acute nor daily administration of 8-OH-DPAT changed levels of HVA, DOPAC or MHPG. Large increases in 5-HIAA occurred when chronic 8-OH-DPAT was discontinued but declined within one week to control levels. Following a two-week drug-free period, 8-OH-DPAT again caused a significant reduction in 5-HIAA levels.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Neurochemical changes in pigeon cerebrospinal fluid during chronic administration of buspirone or 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). 247 84

The effects of drugs that bind selectively to different serotonin (5-HT) receptor subtypes were assessed in pigeons. Keypecking was maintained by a multiple fixed-ratio schedule of reinforcement in which responding also was punished during one component. The greatest increases in punished responding were produced by the buspirone analogs BMY 7378 and ipsapirone, which act at the 5-HT1A receptor. RU 24969, with high affinity for both 5-HT1A and 5-HT1B receptors, and 1-(2-methoxyphenyl)piperazine, a 5-HT1 compound, increased punished responding to a lesser extent, as did the 5-HT2 antagonists ketanserin and ritanserin. The 5-HT3 antagonists GR 38032F, ICS 205930 and MDL 72222 showed little systematic effect, and the mixed 5-HT1B/5-HT1C compound 1-(3-chlorophenyl)piperazine produced only decreases in punished responding. Levels of neurotransmitter metabolites in cerebrospinal fluid were assessed across a wide dose range of representative drugs used in the behavioral studies. Levels of the 5-HT metabolite 5-hydroxyindoleacetic acid were decreased significantly by BMY 7378 and ipsapirone, were not changed by ritanserin and were increased at one dose by MDL 72222. The results are consistent with suggestions that decreased 5-HT neurotransmission is involved in the effects of novel nonbenzodiazepine anxiolytics such as buspirone. Behavioral and neurochemical data also indicate that the effects of these drugs on other neurotransmitter systems do not play a significant role in their anxiolytic actions.
 ...
PMID:Behavioral studies with anxiolytic drugs. VI. Effects on punished responding of drugs interacting with serotonin receptor subtypes. 247 47

In vivo dialysis coupled to high-performance liquid chromatography with electrochemical detection (HPLC-EC) was used for measurement of extracellular serotonin (5-HT) in the hypothalamus of unanesthetized, unrestrained rats. A series of experiments was carried out to determine if 5-HT in the dialysis solution was released from nerve terminals. Fenfluramine, a 5-HT-releasing drug and fluoxetine, a 5-HT-reuptake inhibitor, both significantly increased extracellular 5-HT. Elevating potassium concentration in the dialysis solution also significantly increased 5-HT. Reciprocally, 5-HT was significantly reduced to about half of control levels with either local administration of tetrodotoxin, zero calcium dialysis solution, or systemic administration of 8-hydroxy-2-(di-n-propylamino)tetralin, a 5-HT1A agonist that suppresses 5-HT neuronal activity via activation of the somatodendritic autoreceptor. In addition, 5-HT levels were elevated during the dark portion of the light-dark cycle, a period when rats are more active. Changes in extracellular 5-hydroxyindoleacetic acid (5-HIAA) rarely followed changes in 5-HT. The results indicate that 5-HT in the dialysis solution, but not 5-HIAA, was a reliable measure of depolarization-induced release of 5-HT from nerve terminals. This is the first report establishing the reliability of in vivo dialysis coupled to HPLC-EC for measurement of synaptically released 5-HT.
 ...
PMID:Extracellular serotonin and 5-hydroxyindoleacetic acid in hypothalamus of the unanesthetized rat measured by in vivo dialysis coupled to high-performance liquid chromatography with electrochemical detection: dialysate serotonin reflects neuronal release. 247 59

Evolutionary constant serotonin (5-HT) neuronal systems evolved along medial brain structures; yet, wide variations in functionality characterize serotonergic systems in mediating aggressive responses in species ranging from lobsters, ants, electric fish, and rodents to primates. So far, the attempts to correlate cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) levels with measures of aggression have revealed inverse, direct, or no correlations in different nonhuman primate species. It is difficult to harmonize the occasional correlations between CSF 5-HIAA and adaptive aggressive acts in nonhuman primates (a) with clinically diagnosed suicidal or impulsive individuals, and (b) with the biochemical, anatomical, and presumably functional differentiation of 5-HT pathways and receptor subtypes. Eltoprazine, a mixed 5-HT1A/B agonist, and meta-trifluoro-methylphenyl-piperazine HCl (TFMPP), a more selective 5-HT1B agonist, specifically decrease aggressive behavior in several animal species and situations in both sexes without detriment to other social, exploratory, or motoric activities. A definite role for 5-HT1A, 5-HT2, and 5-HT3 receptor subtypes in the mechanisms mediating aggressive behaviors has to await the development of selective agonists and antagonists, respectively.
 ...
PMID:Brain 5-HT and inhibition of aggressive behavior in animals: 5-HIAA and receptor subtypes. 248 73

The effects of microinfusion of serotonin (5-HT) agents as well as glutamate and muscimol into the ventral tegmental area (VTA) on dopamine (DA) release in the ipsilateral nucleus accumbens (ACC) were investigated in freely moving rats, using a push-pull perfusion procedure. The baseline values for DA, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were approximately 0.24, 8.4, 2.1 and 2.7 pmol/15 min, respectively, in the push-pull perfusate of the ACC. When microinfused into the VTA, glutamate (0.74 microgram) significantly (p less than 0.05) increased the contents of DOPAC (110%) and HVA (90%) over baseline levels in the perfusate. On the other hand, 0.5 microgram muscimol (a gamma-amino-n-butyric acid, GABA, agonist) significantly, (p less than 0.05) decreased both DA (40%) and DOPAC (20%) levels relative to baseline values. Administration of 2 micrograms 5-HT into the VTA caused a significant (p less than 0.05) elevation in the perfusate levels of DOPAC (80%) and HVA (70%) over baseline values. A similar effect was obtained with a nonselective 5-HT1 agonist but not with a selective 5-HT1A agonist. The results suggest that 5-HT innervations in the VTA may have an excitatory action possibly via 5-HT1B rather than 5-HT1A receptors on the mesolimbic DA system projecting to the ACC and that this DA system may also be regulated by glutamatergic and GABAergic (via GABAA receptors) inputs.
 ...
PMID:Serotonin microinfusion into the ventral tegmental area increases accumbens dopamine release. 257 44

The racemic mixture of 3,4-methylenedioxymethamphetamine (MDMA), which has been reported to produce selective destruction of serotonergic neurons in the central nervous system, was studied to determine its neuroendocrine and temperature effects and mechanism of action. MDMA elevated serum concentrations of corticosterone in doses ranging from 3 to 20 mg/kg administered i.p. Serum corticosterone concentrations were elevated 30 min after the administration of MDMA (10 mg/kg i.p.) and remained elevated 4 hr later. Serum prolactin (PRL) concentrations were elevated by administration of MDMA in doses ranging from 1 to 20 mg/kg i.p., and were maximal 60 min after the injection of 10 mg/kg i.p., declining rapidly over the next 4 hr. MDMA also significantly elevated the body temperature of rats maintained at ambient (23 degrees C) temperature. MDMA-induced corticosterone secretion and hyperthermia were blocked by the 5-hydroxytryptamine (5-HT) antagonists, ketanserin and mianserin, which have a high affinity for 5-HT2 binding sites. Conversely, neither (-)-pindolol, a beta antagonist that also blocks 5-HT1A-mediated responses, nor the nonspecific 5-HT antagonists, cyproheptadine and metergoline, had an effect on MDMA-induced corticosterone secretion. None of the 5-HT antagonists blocked MDMA-induced PRL secretion. Pretreatment with fluoxetine (10 mg/kg i.p.) 16 hr before MDMA administration significantly blunted the effect of MDMA on corticosterone but not PRL secretion. Pretreatment with p-chlorophenylalanine (150 mg/kg i.p.) for 3 days depleted cortical and hypothalamic 5-HT and 5-hydroxyindoleacetic acid by approximately 80% and significantly attenuated MDMA-induced corticosterone and PRL secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Elevation of serum prolactin and corticosterone concentrations in the rat after the administration of 3,4-methylenedioxymethamphetamine. 289 23

A superfusion system employed to measure the K+-stimulated release of [3H]5-hydroxytryptamine [(3H]5-HT, [3H]serotonin) from a synaptosomal-rich spinal cord tissue preparation was carefully characterized, then used to examine the regulation of spinal 5-HT release. Spinal 5-HT release is apparently modulated by an autoreceptor. Exogenous 5-HT depressed, in a concentration-dependent manner, the K+-stimulated release of [3H]5-HT. Similarly, lysergic acid diethylamide (LSD) produced a concentration-dependent decrease in [3H]5-HT release. Methiothepin and quipazine blocked the inhibition of release induced by exogenous 5-HT. The 5-HT2 receptor antagonists spiperone and ketanserin failed to alter the action of 5-HT at the spinal 5-HT autoreceptor. Spiperone and ketanserin were shown, however, to alter the storage of [3H]5-HT. When used in concentrations greater than 10 nM, the drugs evoked increases in basal [3H]5-HT and [3H]5-hydroxyindoleacetic acid ( [3H]5-HIAA) effluxes which were independent of the presence of calcium ions. A good agreement existed between the potencies of drugs for modifying autoreceptor function and their abilities to compete for high-affinity [3H]5-HT binding in the spinal cord (designated 5-HT1). Furthermore quipazine, in concentrations that preferentially interact with the 5-HT1B subtype, antagonized the actions of exogenous 5-HT on K+-stimulated release. Spiperone, in a concentration that approximated the affinity constant of 5-HT1A sites for the drug, was ineffective in altering the ability of exogenous 5-HT to modulate K+-stimulated [3H]5-HT release. These results suggest that 5-HT1B sites are associated with serotonergic autoreceptor function in the spinal cord.
 ...
PMID:Demonstration of an autoreceptor modulating the release of [3H]5-hydroxytryptamine from a synaptosomal-rich spinal cord tissue preparation. 387 46

Male Sprague-Dawley rats received injections of cocaine (20 mg/kg/dose, IP) every 12 h for 14 days and were sacrificed on the 15th day. The chronic cocaine treatment caused an increase in the levels of serotonin [5-hydroxytryptamine (5-HT)] and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the hippocampus. 5-HIAA levels in the frontal cortex were also increased, but 5-HT levels were unaltered by the chronic cocaine treatment. Similarly, striatal levels of 5-HT and 5-HIAA were unchanged by repeated administration of cocaine. Chronic cocaine administration did not alter the density of [3H]8-OH(DPAT), [3H]mesulergine, or [3H]ketanserin binding in the hippocampus, choroid plexus, and frontal cortex, respectively. Furthermore, repeated injection of cocaine did not alter serotonergic-mediated inhibition of adenylate cyclase activity. Thus, repeated administration of cocaine causes region-specific alterations in 5-HT levels but does not change the properties of the 5-HT1A, 5-HT1C, or 5-HT2 receptors.
 ...
PMID:Effects of chronic cocaine administration on the serotonergic system in the rat brain. 750 54

Morphological evidence demonstrates the existence of dopaminergic afferent pathways and dopamine (DA)-containing neurons in the dorsal raphe nucleus (DRN). In a recent report, a DA D2-like receptor-mediated regulation of serotonin (5-HT) extracellular concentration in DRN has been found. Given the existence of somatodendritic 5-HT1A autoreceptors in the DRN, changes of the extracellular concentration of 5-HT in the vicinity of cell bodies and dendrites may be relevant for the control of the activity of ascending serotonergic pathways. In the present brain microdialysis study we have used a chromatographic method (HPLC) enabling the simultaneous measurement of DA, 5-HT, and their main metabolites dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA). The presence of a neuronal pool of DA within the DRN was revealed by the local infusion of amphetamine (10 microM), which significantly increased the extracellular concentration of both amines. The local striatal infusion (10 microM) of the selective DA D1-like agonist SKF-38393, the selective DA D2-like agonist quinpirole (LY 171,555), or the nonselective DA agonist apomorphine markedly decreased DA and DOPAC extracellular concentrations and failed to modify 5-HT or 5-HIAA in the striatum, indicating the lack of terminal (striatal) control of 5-HT release by dopaminergic transmission. In contrast, the systemic administration of apomorphine (2.8 mumol/kg, s.c.) significantly increased the extracellular concentration of 5-HT in the DRN and decreased it in the striatum. The reduction of striatal 5-HT extracellular concentration was prevented by the previous administration of the selective 5-HT1A receptor antagonist WAY 100135 (17.6 mumol/kg, s.c.), which by itself did not change extracellular 5-HT in striatum.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Dopaminergic regulation of the serotonergic raphe-striatal pathway: microdialysis studies in freely moving rats. 751 57

The effect of chronic treatment with a tryptophan (TRP)-free diet on the free-running circadian wheel-running rhythm and the central serotonergic system was investigated in blinded male rats. The long-term TRP-free diet did not change periods of activity, but disordered their patterns. This seemed to be due to masking, entrainment, enhancement of the morning activity, and obscuring of the activity onset as well as appearance of some periodic activities within the subjective night. A long-term TRP-fre diet decreased the concentration of TRP, 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in all brain regions tested: frontal cortex, hippocampus, thalamus, hypothalamus, midbrain, and pons. Density of 5-HT1A receptor binding was significantly decreased in the frontal cortex and hypothalamus, whereas no significant change was observed in the density of 5-HT2 receptor binding in all regions. These results suggest that the period of primary circadian pacemaker is not affected, but its oscillation, as well as the coupling strength between the primary and secondary pacemakers, is weakened by the dysfunction of the serotonergic system caused by chronic TRP depletion.
 ...
PMID:Effect of chronic tryptophan depletion on the circadian rhythm of wheel-running activity in rats. 751 51


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