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1.
The role of serotonin axons in modulating the norepinephrine neurotransmission system in rat brain was investigated. Selective lesions of the forebrain serotonergic system were made by injecting 5,7-dihydroxytryptamine into the midbrain raphe nuclei. Four to six weeks after the lesion, the uptake of 3H-labeled serotonin in the frontal cortex and the hippocampus was reduced by more than 90 percent, while neither the uptake of 3H-labeled norepinephrine nor the content of norepinephrine was affected in either tissue. The number of beta-adrenergic receptors, as measured by radioligand binding with 3H-labeled dihydroalprenolol, was increased in the frontal cortex and hippocampus of rats with lesions. Similarly, specific lesions of central serotonin axons produced by systemically administered p-chloramphetamine resulted in an increase in the binding of 3H-labeled dihydroalprenolol to beta-adrenergic receptors and in the production of adenosine 3',5'-monophosphate in response to isoproterenol. These results indicate that serotonin axons may regulate beta-adrenergic receptor number and function in brain. 相似文献
2.
Clarke HF Dalley JW Crofts HS Robbins TW Roberts AC 《Science (New York, N.Y.)》2004,304(5672):878-880
Serotonergic dysregulation within the prefrontal cortex (PFC) is implicated in many neuropsychiatric disorders, but the precise role of serotonin within the PFC is poorly understood. Using a serial discrimination reversal paradigm, we showed that upon reversal, selective serotonin depletion of the marmoset PFC produced perseverative responding to the previously rewarded stimulus without any significant effects on either retention of a discrimination learned preoperatively or acquisition of a novel discrimination postoperatively. These results highlight the importance of prefrontal serotonin in behavioral flexibility and are highly relevant to obsessive-compulsive disorder, schizophrenia, and the cognitive sequelae of drug abuse in which perseveration is prominent. 相似文献
3.
The effects of short- and long-term administration of morphine on the activity of two measurable forms of rat brain tryptophan hydroxylase were studied. Morphine administration produced an immediate decrease and a longterm increase in the nerve ending (particulate) enzyme activity but did not change the cell body (soluble) enzyme activity. Cocaine administration demnonstrated a short-term decrcease in measurable nerve eniding enzyme activity that was due to the inhibition of the high affinity uptake (the Michaelis constant, K(m) is 10-(5) molar) of trytophan, the serotonin precursor. Cocaine did not aflect the low affinity uptake K(m) = 10-(5) molar) of tryptophan. Both the uptake of the precursor and the enizymiie activity appeared to be drug-sensitive regullatory processes in the biosynthlesis of serotonin. 相似文献
4.
Brain serotonin concentration: elevation following intraperitoneal administration of melatonin 总被引：5，自引：0，他引：5
The intraperitoneal administration of melatonin to rats caused an increase in brain serotonin concentration, especially in the midbrain. This effect could be demonstrated within 20 minutes of melatonin administration and was not associated with changes in norepinephrine concentration. 相似文献
5.
In the pineal body of the immature rat the circadian rhythm of serotonin persists when sympathetic innervation is abolished by the administration of nerve growth factor antiserum. This rhythm is regulated by a mechanism that does not involve the sympathetic innervation and is, therefore, fundamentally different from that in the adult. 相似文献
6.
A soluble form of tryptophan-5-hydroxylase activity was found to be present in areas rich in serotonergic terminals (colliculi, hippocampus, septal area, and remaining telencephalon) as well as in brainstem, an area rich in cell bodies. The enzymatic activity in all brain regions, except the septal area, was inhibited to varying degrees following administration of parachlorophenylalanine. Destruction of the raphe nuclei in the midbrain led to a large and comparable decrease in both serotonin content and tryptophan hydroxylase activity of the hippocampus. In contrast, these lesions did not significantly affect the enzymatic activity of the septal area although the serotonin content was decreased by 72 percent. These findings suggest that the major portion of the tryptophan hydroxylase activity of the septal area is uniquely different from that found in other telencephalic areas in that it is not localized in serotonergic nerve terminals nor is it inhibited by parachlorophenylalanine. 相似文献
7.
Long-term amphetamine administration to cats (a mean of 8.75 milligrams per kilogram twice daily for 10 days) produced large decreases (40 to 67 percent in serotonin and its major metabolite, 5-hydroxyindoleacetic acid, in all brain regions examined. This treatment also produced several behaviors that are dependent on depressed central serotonergic neurotransmission, and which normally are elicited exclusively by hallucinogenic drugs. Short-term amphetamine administration (15 mg/kg) did not produce these behaviors and resulted in small decreases in brain serotonin and no change in 5-hydroxyindoleacetic acid. These data are discussed in the context of monoamine theories of schizophrenia. 相似文献
8.
Long-term antidepressant treatment decreases spiroperidol-labeled serotonin receptor binding 总被引：29，自引：0，他引：29
Antidepressants compete at several neurotransmitter receptor binding site, but drug affinities do not correlate with clinical efficacy. Long-term, but not short-term, antidepressant treatment decreases the numbers of both serotonin and beta-adrenergic receptors. The decrease in the number of receptor sites is most marked for [3H]spiroperidol-labeled serotonin receptors and is characteristic for antidepressants of several classes. 相似文献
9.
Preference for ethyl alcohol was significantly reduced or totally abolished in rats given orally p-chlorophenylalanine, a tryptophan hydroxylase inhibitor that selectively depletes brain serotonin. Some aversion to alcohol was observed while p-chlorophenylalanine was administered, but the rats' rejection of alcohol was even more marked after the drug was discontinued. Oral administration of alpha-methyl-p-tyrosine, a tyrosine hydroxylase inhibitor that depletes brain catecholamines, slightly reduced selection of alcohol, but preference returned to normal as soon as alpha-methyl-p-tyrosine was terminated. 相似文献
10.
When plasma tryptophan is elevated by the injection of tryptophan or insulin, or by the consumption of carbohydrates, brain tryptophan and serotonin also rise; however, when even larger elevations of plasma tryptophan are produced by the ingestion of protein-containing diets, brain tryptophan and serotonin do not change. The main determinant of brain tryptophan and serotonin concentrations does not appear to be plasma tryptophan alone, but the ratio of this amino acid to other plasma neutral amino acids (that is, tyrosine, phenylalanine, leucine, isoleucine, and valine) that compete with it for uptake into the brain. 相似文献
11.
Brain dopamine and serotonin receptor sites revealed by digital subtraction autoradiography 总被引：5，自引：0，他引：5
Autoradiography combined with image analysis permitted quantitative visualization of dopamine (D2) and serotonin (S2) binding sites in rat brain. Forebrain sections were incubated with tritiated spiroperidol alone or with tritiated spiroperidol plus unlabeled compounds that saturated the D2 or S2 sites. By subtracting the digitized image of an autoradiograph derived from the latter sections from that of the former, the D2 or S2 sites were specifically revealed. The resulting quantitative images demonstrate the differing anatomical distributions of these sites. The D2 site is largely restricted to the striatal complex (caudate-putamen, nucleus accumbens septi, and olfactory tubercle), whereas the S2 site is enriched in layer 5 of motor cortex, the perirhinal and cingulate cortices, and the claustrum. 相似文献
12.
Short- and long-term lithium administration: effects on the brain's serotonergic biosynthetic systems 总被引：4，自引：0，他引：4
Short-term treatment with lithium chloride stimulates the uptake of tryptophan and its conversion to serotonin by striate synaptosomes. Preincubation of striate synaptosomes with L-tryptophan and in vivo administration of L-tryptophan appear to act in a similar manner. Midbrain tryptophan hydroxylase activity is reduced in temporal continuity with the lithium-induced activation of tryptophan uptake and conversion. By 10 days, conversion of tryptophan to serotonin in nerve endings becomes a joint function of the maintained increased uptake of tryptophan and a decreased level of tryptophan hydroxylase activity in nerve endings. The occurrence of this delayed alteration corresponds in time to the previously described axoplasmic flow rate for tryptophan hydroxylase. 相似文献
13.
Rats with electrodes implanted in the medial forebrain bundle stimulated their own brains at sharply reduced rates after systemic administration of disulfiram or intraventricular administration of diethyldithiocarbamate. Both drugs inhibit dopamine-beta-hydroxylase, the enzyme responsible for the final step in the biosynthesis of norepinephrine. The suppressed behavior was reinstated by intraventricular injections of 1-norepinephrine, but not by injection of its biologically inactive isomer, d-norepinephrine. Intraventricular administration of dopamine and serotonin did not restore self-stimulation. The rewarding effect of medial forebrain bundle stimulation may depend on the availability of norepinephrine as a transmitter, but not on dopamine or serotonin. 相似文献
14.
Cyclic adenosine monophosphate: stimulation of melatonin and serotonin synthesis in cultured rat pineals 总被引：3，自引：0，他引：3
Dibutyryl cyclic adenosine monophosphate, like norepinephrine, stimulates the synthesis of labeled melatonin and serotonin from tryptophan labeled with carbon-14 by rat pineals in organ culture. Unlike norepinephrine, dibutyryl cyclic adenosine monophosphate does not enhance the accumulation of labeled tryptophan or protein within the pineal. These findings are compatible with the hypothesis that cyclic adenosine monophosphate mediates some, but not all, of the effects of norepinephrine. 相似文献
15.
Lesurtel M Graf R Aleil B Walther DJ Tian Y Jochum W Gachet C Bader M Clavien PA 《Science (New York, N.Y.)》2006,312(5770):104-107
The liver can regenerate its volume after major tissue loss. In a mouse model of liver regeneration, thrombocytopenia, or impaired platelet activity resulted in the failure to initiate cellular proliferation in the liver. Platelets are major carriers of serotonin in the blood. In thrombocytopenic mice, a serotonin agonist reconstituted liver proliferation. The expression of 5-HT2A and 2B subtype serotonin receptors in the liver increased after hepatectomy. Antagonists of 5-HT2A and 2B receptors inhibited liver regeneration. Liver regeneration was also blunted in mice lacking tryptophan hydroxylase 1, which is the rate-limiting enzyme for the synthesis of peripheral serotonin. This failure of regeneration was rescued by reloading serotonin-free platelets with a serotonin precursor molecule. These results suggest that platelet-derived serotonin is involved in the initiation of liver regeneration. 相似文献
16.
As the interface between hippocampus and neocortex, the entorhinal cortex is likely to play a pivotal role in memory. To determine how information is represented in this area, we measured spatial modulation of neural activity in layers of medial entorhinal cortex projecting to the hippocampus. Close to the postrhinal-entorhinal border, entorhinal neurons had stable and discrete multipeaked place fields, predicting the rat's location as accurately as place cells in the hippocampus. Precise positional modulation was not observed more ventromedially in the entorhinal cortex or upstream in the postrhinal cortex, suggesting that sensory input is transformed into durable allocentric spatial representations internally in the dorsocaudal medial entorhinal cortex. 相似文献
17.
Primary cultures of astrocytes from neonatal rat brain were incubated with tritiated serotonin. After fixation they were stained by immunofluorescence for the astrocyte-specific marker glial fibrillary acidic protein and processed for autoradiography. Silver grain density was increased over cells positive for glial fibrillary acidic protein and was reduced to background levels when sodium was omitted from the medium or the specific inhibitors of serotonin uptake fluoxetine and chlorimipramine were present. The results indicate that mammalian astrocytes can take up serotonin by a sodium-dependent, high-affinity system previously thought to be the exclusive property of serotonergic nerve endings. 相似文献
18.
Sleep patterns of the monkey and brain serotonin concentration: effect of p-chlorophenylalanine 总被引：2，自引：0，他引：2
The amount of time that monkeys (Macaca mulatta) slept was reduced after they were given p-chlorophenylalanine, a selective depletor of serotonin in animal tissues. The time spent in the rapid eye movement stage of sleep was unchanged, but the time in other sleep stages decreased. Seven regions of the brain had a 31 to 46 percent decrease in serotonin content; the concentration of cerebellar serotonin increased by 44 percent. 相似文献
19.
(+/-)-3,4-Methylenedioxyamphetamine (MDA), an amphetamine analog with hallucinogenic activity, produced selective long-lasting reductions in the level of serotonin, the number of serotonin uptake sites, and the concentration of 5-hydroxyindoleacetic acid in rat brain. Morphological studies suggested that these neurochemical deficits were due to serotonin nerve terminal degeneration. These results show that MDA has toxic activity for serotonin neurons in rats and raise the question of whether exposure to MDA and related hallucinogenic amphetamines can produce serotonin neurotoxicity in the human brain. 相似文献
20.
Ectopic expression of the serotonin 1c receptor and the triggering of malignant transformation 总被引：31，自引：0，他引：31
Neurotransmitter receptors are usually restricted to neuronal cells, but the signaling pathways activated by these receptors are widely distributed in both neural and non-neural cells. The functional consequences of activating a brain-specific neurotransmitter receptor, the serotonin 5HT1c receptor, in the unnatural environment of a fibroblast were examined. Introduction of functional 5HT1c receptors into NIH 3T3 cells results, at high frequency, in the generation of transformed foci. Moreover, the generation and maintenance of transformed foci requires continued activation of the serotonin receptor. In addition, the injection of cells derived from transformed foci into nude mice results in the generation of tumors. The serotonin 5HT1c receptor therefore functions as a protooncogene when expressed in NIH 3T3 fibroblasts. 相似文献