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1.
The effects of CNS monoamine depletion on audiogenic seizure (AGS) susceptibility and intensity were studied in two types of Sprague-Dawley derived rats: (1) the progeny of a nonsusceptible strain (controls); and (2) the nonsusceptible progeny of epilepsy-prone (audiogenic seizure susceptible) parents (NSPSP). Forty-five minutes after injection of the benzoquinolizine Ro 4-1284, a significant fraction of the NSPSP developed AGS susceptibility, whereas the incidence in controls was not significant. AGS intensity was also significantly elevated 45 minutes and 19 days following Ro 4-1284 in NSPSP. In controls, there was a smaller, but significant, elevation of seizure intensity only at the earlier time period. Both types of rats exhibited a marked depletion of norepinephrine (NE) and 5-hydroxytryptamine (5-HT) in all of the six different areas of the CNS which were examined. In the NSPSP, a significant incidence of seizure susceptibility was retained as long as 19 days after Ro 4-1284 administration, despite the complete repletion of monoamine stores. These observations suggest that CNS monoaminergic neurons function as determinants of AGS susceptibility and intensity in animals which also carry some other genetically determined susceptibility factor(s). A deficiency in monoaminergic transmission is insufficient to cause susceptibility in animals not carrying the other trait(s). Also, although a monoaminergic deficit may initially cause the appearance of susceptibility, the presence of the deficit may not be necessary for the continuation of susceptibility once an animal has actually sustained an AGS in the presence of the monoaminergic deficit. 相似文献
2.
Ca2+-ATPase activity was studied in fresh brain stem homogenates of the audiogenic seizure (AGS)-resistant C57BL/6 and AGS-susceptible DBA/2 inbred strains and in 21 B6 X D2 recombinant inbred strains. A highly significant negative correlation was found between Ca2+-ATPase activity and AGS susceptibility among these strains. In general, strains with low Ca2+-ATPase activities were more AGS-susceptible than strains with high activities. Further, Ca2+-ATPase activity appears to be influenced by a major gene associated with the Ah locus. This gene is designated Caa for Ca2+-ATPase activity and is different from Ias, which is closely linked to the Ah locus. Ias influences AGS spread by a yet unknown biochemical mechanism, whereas Caa may influence AGS susceptibility by regulating Ca2+-ATPase activity in brain tissue. 相似文献
3.
Gary L. Brookhart Robert S. Edgecomb Larry L. Murdock 《Journal of neurochemistry》1987,48(4):1307-1315
HPLC with electrochemical detection was used to determine the levels of p-hydroxyphenylethanolamine (octopamine), 3,4-dihydroxyphenylethylamine (dopamine), and 5-hydroxytryptamine (5-HT) in the brains of control, reserpine, and d-amphetamine-treated blow flies, Phormia regina Meigen. Parallel studies were carried out to assess the effects of the two drugs on fly feeding behavior, measured as mean acceptance threshold: the minimum sucrose concentration to which the average fly in a population will respond by proboscis extension when its tarsi contact the solution. In saline-injected control flies, all three amines were found at levels of approximately 2 pmol/brain. Thirty minutes after injection with d-amphetamine (12 micrograms/fly), brain octopamine was depleted by 85%, whereas dopamine and 5-HT were depleted by 70%. Reserpine (5 micrograms/fly) caused 70% depletion of dopamine and greater than 90% depletion of both octopamine and 5-HT 24 h after injection. However, the effect of reserpine was much slower in onset (hours versus minutes) and more persistent (days versus hours) than was the effect of d-amphetamine. With either drug, the time course of amine depletion closely matched the time course of the increase in feeding threshold observed in drug-treated flies. These results suggest that CNS pools of the biogenic amines, octopamine, dopamine, and 5-HT are important in governing blow fly responsiveness to food stimuli. 相似文献
4.
Effect of p-chlorophenylalanine on development of cross-tolerance between pentobarbital and ethanol.
D Frankel J M Khanna A E LeBlanc H Kalant 《Canadian journal of physiology and pharmacology》1977,55(4):954-957
Rats developed cross-tolerance to the motor-impairing effects of ethanol after daily oral administration of pentobarbital. Chronic administration of p-chlorophenylalanine (p-CPA), in a dosage regimen previously demonstrated to maintain extensive brain serotonin (5-HT) depletion, slowed down cross-tolerance development. p-CPA did not appear to exert this effect by altering the disposition of ethanol, since blood ethanol levels measured 20 min after ethanol administration were not affected by p-CPA treatment. This study extends our previous findings with respect to the inhibitory effects of p-CPA on tolerance development to ethanol and pentobarbital, and suggests that 5-HT may play a role in cross-tolerance development between ethanol and pentobarbital. 相似文献
5.
The pharmacological effects of GABA-related drugs were studied on the serotonin (5-HT) and 5-hydroxyindole-acetic acid (5-HIAA) contents of various regions of the rat brain. These effects were examined in the nuclei raphe dorsalis, magnus and centralis and in structures receiving a dense serotonin innervation such as the habenula complex and subcommissural organ. The GABA agonist, muscimol, increased the 5-HT contents and reduced 5-HIAA levels in structures containing serotoninergic terminals suggesting an inhibitory effect of GABA on the firing of serotoninergic neurons with concomitant reduction of 5-HT utilisation. In contrast, the GABA antagonist, bicuculline, probably stimulated 5-HT turnover since its intraperitoneally administration produced significant increase of 5-HT and/or 5-HIAA levels in the same brain regions. These data are in agreement with a transsynaptic inhibitory control of GABA on serotoninergic neurons. Drugs which inhibit the GABA catabolism such as amino-oxyacetic acid or gamma-vinyl-GABA and which should elevate GABA levels in the synaptic gap were capable of increasing or decreasing the 5-HT and the 5-HIAA levels depending on the experimental conditions. These results suggest that several processes are probably involved in the control of serotoninergic neurons by GABA in the rat brain. Among them, an intracellular effect of GABA on 5-HT metabolism might well occur in cells containing both GABA and 5-HT. 相似文献
6.
In recent years, there has been increasing evidence that serotonergic neurotransmission modulates a wide variety of experimentally induced seizures. Generally, agents that elevate extracellular serotonin (5-HT) levels, such as 5-hydroxytryptophan and serotonin reuptake blockers, inhibit both focal and generalized seizures, although exceptions have been described, too. Conversely, depletion of brain 5-HT lowers the threshold to audiogenically, chemically and electrically evoked convulsions. Furthermore, it has been shown that several anti-epileptic drugs increase endogenous extracellular 5-HT concentration. 5-HT receptors are expressed in almost all networks involved in epilepsies. Currently, the role of at least 5-HT(1A), 5-HT(2C), 5-HT(3) and 5-HT(7) receptor subtypes in epileptogenesis and/or propagation has been described. Mutant mice lacking 5-HT(1A) or 5-HT(2C) receptors show increased seizure activity and/or lower threshold. In general, hyperpolarization of glutamatergic neurons by 5-HT(1A) receptors and depolarization of GABAergic neurons by 5-HT(2C) receptors as well as antagonists of 5-HT(3) and 5-HT(7) receptors decrease the excitability in most, but not all, networks involved in epilepsies. Imaging data and analysis of resected tissue of epileptic patients, and studies in animal models all provide evidence that endogenous 5-HT, the activity of its receptors, and pharmaceuticals with serotonin agonist and/or antagonist properties play a significant role in the pathogenesis of epilepsies. 相似文献
7.
Different technical, physiological and biochemical aspects concerning the study of the release of 5-HT are discussed herein. Isotopic methods are the most suitable techniques since these allow the release of 3H-5-HT to be measured after having determined the identity of the labelled compounds formed from 3H-tryptophan by co-chromatography. Under these conditions, the 3H-amine released in the superfusates comes from serotoninergic nerve endings, since tryptophan hydroxylase is exclusively localized in serotoninergic neurons. Moreover, it appears that newly synthesized 5-HT is preferentially released. The release of 5-HT is dependent on neuronal activity, but is not always linked to the synthesis of 5-HT. The increase in the firing rate of serotoninergic cell bodies by a local application of glutamate in the area of the nucleus raphe dorsalis induces a marked increase n the release of 5-HT in the caudate nucleus; an opposite effect is observed after cooling this region. The local depolarization of serotoninergic terminals located in the caudate nucleus increases the release of this amine. This effect is blocked by TTX. LSD reduces the stimulating effect of KCl, thus indicating that the release of 5-HT can be controlled at a presynaptic level. In addition, the release of the amine is dependent on the presence of calcium. Serotoninergic neuronal activity can be controlled at the preterminal or at the cell body levels by the activity of other neuronal systems. The effects of the release of dopamine from dendrites, and that of GABA in the substantia nigra are reported herein. Furthermore, changes in the activity of the dopaminergic, gabaergic and serotoninergic systems innervating the nucleus raphe dorsalis modulate the release of 5-HT, measured both in the caudate nucleus and in the nucleus raphe magnus. Finally, it has been reported that the release of 5-HT can be estimated in the raphe nuclei dorsalis and magnus. It has been shown that the amounts of 3H-5-HT continuously formed from 3H-TRP and released in the nucleus raphe dorsalis are much greater than those estimated in the caudate nucleus or in the substantia nigra. Although the quantities of endogenous 5-HT measured in the nucleus raphe dorsalis are the highest in the brain, this structure presents only a few serotoninergic nerve endings. This raises the question of the origin of the 5-HT released in serotoninergic nuclei. A possible dendritic release of 5-HT is discussed. 相似文献
8.
Tadashi Asakura Naoto Takahashi Tae Hirakawa Kiyoshi Ohkawa Nozomu Hibi 《Neurochemical research》1996,21(1):47-50
We investigated the relationship between the concentration of pyridoxal-5′-phosphate (PLP) and biogenic amine in mouse brain.
The production of PLP from pyridoxal (PL) by pyridoxal kinase (PLK) was inhibited by the addition of dopamine (DA), norepinephrine
(NE) and 5-hydroxytryptamine (5-HT), but not by that of epinephrine and N-acetyl-serotonin. DA and NE were combined with PLP
by a non-enzymatic reaction, whereas 5-HT was bound only slightly with PLP. The conjugated product of PLP with DA was also
detected by HPLC analysis when PLK activity was assayed using PL as a substrate in the presence of DA. In an in vivo investigation,
the depletion of DA and 5-HT in mouse brain after an intraperitoneal injection of 5 mg/kg reserpine, led to slight elevation
of the PLP level to 120% of the control level. By contrast, the increase in DA in the brain caused by intraperitoneal administration
of 150 mg/kg L-DOPA caused the PLP concentration to decrease to 70% of the control level. However, no change in PLK activity
in the brain was observed when the mice were treated with either reserpine or L-DOPA. These results suggested that the level
of PLP in mouse brain was partly regulated by the concentration of biogenic amines, such as DA, NE and 5-HT, without apparent
induction of PLK. 相似文献
9.
David J. Taylor Gene E. Robinson Barbara J. Logan Richard Laverty Alison R. Mercer 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1992,170(6):715-721
Summary Changes in biogenic amine levels associated with the morphological and behavioural development of the worker honeybee are examined.A significant increase in amine levels in the head of the honeybee is associated with transition from the larval to pupal stage. Adult emergence is also accompanied by a significant increase in 5-HT levels in the brain, but no significant change in brain dopamine (DA) levels. NADA (N-acetyldopamine) levels increase during larval and pupal development, but in contrast to both DA and 5-HT, drop significantly during the transition from pupa to adult.Levels of DA in the brain of nectar and pollen forager bees, presumed to be among the oldest adults sampled, were found to be significantly higher than in nurses, undertakers or food storers. These results suggest that an age-dependent change in amine levels occurs in the brain of the worker bee. In the optic lobes, levels of DA and 5-HT were found to be significantly higher in pollen forager bees than in all other behavioural groups. Significant differences in amine levels in the optic lobes of nectar foragers and pollen foragers indicate that some differences in amine levels occur independent of worker age. The functional significance of differences in brain amine levels and whether or not biogenic amines play a direct role in the control of honeybee behaviour has yet to be established.Abbreviations
DA
dopamine
-
5-HT
5-hydroxytryptamine or serotonin
-
NADA
N-acetyldopamine 相似文献
10.
Intravenous L-DOPA caused a dose-dependent depletion of 5-HT in the lumbar region of rat spinal cord. Pretreatment with the peripheral decarboxylase inhibitor MK-486, significantly increased the 5-HT-depleting effect of acutely administered L-DOPA. Chronically administered L-DOPA (100 mg/kg per day for 3 days) had no effect on spinal 5-HT levels 24 hours after the last dose. It is concluded that the L-DOPA-mediated depletion of 5-HT from serotonergic terminals, already demonstrated to occur in the brain, also occurs in the spinal cord. This released 5-HT could be involved in mediating some of the observed physiological effects of L-DOPA in the spinal cord. 相似文献
11.
D F Avgustinovich T V Lipina N N Kudriavtseva 《Rossi?skii fiziologicheski? zhurnal imeni I.M. Sechenova / Rossi?skaia akademiia nauk》2001,87(4):532-542
The effects of social stress caused by experience of defeats in mice during 3 or 10 consecutive days of intermale confrontations on serotonergic brain activity (5-HT, 5-HIAA levels and 5-HIAA/5-HT ratio) in some brain regions of CBA/Lac (CBA) and C57BL/6J (C57) inbred mice have been studied. It was revealed the significant changes in 5-HT methabolism in the brain regions of defeated mice (losers) of CBA strain after 3 intermale confrontations. However, after 10 days of social stress these changes (excluded amygdala) turned to the control measures testifying to the adaptive mechanisms of serotonergic system in CBA losers. In C57 strain, the three-day social stress produced the mild changes in the brain serotonergic activity both quantitatively as well as qualitatively. Nevertheless, losers subjected to ten-day intermale confrontations had more expressed changes in 5-HT, 5-HIAA levels of 5-HIAA/5-HT ratios in the brain regions studied. It seems that long lasting social stress induced the development of disbalance of the brain serotonergic activity in C57 losers: it was shown the hyperactivity in the hypothalamus and hypoactivity in the amygdala and nucl. accumbens. Apparently, this cause leads to the development of the pronounced anxiety shown earlier in this mouse strain. 相似文献
12.
Hernandez-Rauda R Aldegunde M 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2002,172(8):659-667
This study investigated: (a) the effects of acute 17alpha-methyltestosterone (MT) or 17beta-estradiol (E(2)) administration on norepinephrine (NE), dopamine (DA), serotonin (5-HT), 3,4, dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) contents in the hypothalamus, telencephalon and pituitary of previtellogenic female rainbow trout Oncorhynchus mykiss, and (b) the effects of chronic MT administration on the levels of these neurotransmitters in these brain regions in immature male rainbow trout. The acute administration of MT induced a significant decrease in pituitary levels of DOPAC as well as in the DOPAC/DA ratio. On the other hand, the acute administration of E(2) induced an increase in pituitary 5-HT levels as well as a decrease in the 5-HIAA/5-HT ratio. In a second experiment, 20 mg MT per kilogram body weight was implanted for 10, 20 or 40 days into sexually immature male rainbow trout. Implanted rainbow trout showed increased testosterone and decreased E(2) levels. In the pituitary, MT induced long-term decreases in NE, DA, DOPAC and 5-HT levels, as well as in the DOPAC/DA ratio. Hypothalamic and telencephalic DA, NE and 5-HT levels were not affected by MT implantation. However, 5-HIAA levels and the 5-HIAA/5-HT ratio were reduced by MT implantation in both brain regions. These results show that chronic treatment with MT exerts both long-term and region-specific effects on NE, DA, and 5-HT contents and metabolism, and thus that this androgen could inhibit pituitary catecholamine and 5-HT synthesis. A possible role for testosterone in the control of pituitary dopaminergic activity and gonadotropin II release is also discussed. 相似文献
13.
I Gil-ad F Zambotti M O Carruba L Vicentini E E Müller 《Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)》1976,151(3):512-518
Systemic administration of parachlorophenylalanine (PCPA, 100 mg/kg sc on alternate days X two times), a blocker of serotonin (5-HT) synthesis, considerably decreased brain 5-HT and plasma prolactin (PRL) levels in young male rats. Intraventricular (IVT) administration of 5,7-dihydroxytryptamine (5,7-DHT, 200 mug/20 mul), a neurotoxic drug which destroys 5-HT nerve terminals, induced, 3, 12, and 30 days after treatment, a marked depletion of brain 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) and considerably reduced plasma PRL levels at each time interval. Feeding of rat for up to 4 days with a tryptophan (TP)-deficient diet, caused a depletion of brain 5-HT and 5-HIAA contents and did not modify plasma PRL levels. Addition of TP (2 g/kg of diet) to the TP-deficient diet resulted in increased brain 5-HT and 5-HIAA contents and significantly increased PRL levels. These data provide evidence for the role of the 5-HT system in the maintenance of tonic PRL secretion. 相似文献
14.
The effects of the organophosphate acetylcholinesterase (AChE) inhibitor soman (31.2 micrograms/kg s.c.) on guinea-pig brain AChE, transmitter, and metabolite levels were investigated. Concentrations of acetylcholine (ACh) and choline (Ch), noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT), and their metabolites, and six putative amino acid transmitters were determined concurrently in six brain regions. The brain AChE activity was maximally inhibited by 90%. The ACh content was elevated in most brain areas by 15 min, remaining at this level throughout the study. This increase reached statistical significance in the cortex, hippocampus, and striatum. The Ch level was significantly elevated in most areas by 60-120 min. In all regions, levels of NA were reduced, and levels of DA were maintained, but those of its metabolites increased. 5-HT levels were unchanged, but those of its metabolites showed a small increase. Changes in levels of amino acids were restricted to those areas where ACh levels were significantly raised: Aspartate levels fell, whereas gamma-aminobutyric acid levels rose. These findings are consistent with an initial increase in ACh content, resulting in secondary changes in DA and 5-HT turnover and release of NA and excitatory and inhibitory amino acid transmitters. This study can be used as a basis to investigate the effect of toxic agents and their treatments on the different transmitter systems. 相似文献
15.
Rat brain cortex slices preincubated with 3H-5-hydroxytryptamine (3H-5-HT) were superfused with physiological salt solution containing paroxetine, an inhibitor of 5-hydroxytryptamine (5-HT) uptake. The effects of various indolethylamines on the electrically evoked tritium overflow (containing 66.3% unmetabolized 3H-5-HT) were investigated (the percentage of unmetabolized 3H-5-HT was not altered by the indolethylamines or metitepin). 6,7-Dihydroxytryptamine (6,7-DHT) did not affect the stimulation-evoked tritium overflow, whereas the latter was inhibited by the other tryptamine derivatives investigated; when the compounds were compared to each other on the basis of their inhibitory potencies the following rank order was obtained: unlabelled 5-HT > 5-methoxytryptamine > 4-HT > 6-HT > 5,6-DHT > tryptamine > 7-HT > 5,7-DHT. The inhibitory effects of these compounds were antagonized by metitepin. It is concluded that the indolethylamines inhibit the stimulation-evoked 3H-5-HT release by activating the presynaptic 5-HT autoreceptors on the 5-HT neurones of the rat brain cortex. Similarities may exist between these receptors and the postsynaptic 5-HTl binding sites of this brain area. 相似文献
16.
Effects of Iron Deficiency on Serotonin Uptake In Vitro by Rat Brain Synaptic Vesicles 总被引:1,自引:1,他引:0
Abstract: The effects of moderate and severe degrees of iron deficiency on brain and liver nonhaem iron levels and 5-hydroxytryptamine (serotonin; 5-HT) uptake by synaptic vesicles in vitro were investigated in experimental rats. Data obtained suggested that in both moderate and severe forms of iron deficiency, 5-HT uptake by brain synaptic vesicles is decreased and is accompanied by a reduction in brain and liver nonhaem iron levels. On repletion with iron for 4 weeks, the deficient group of rats showed a normalisation of 5-HT uptake by synaptic vesicles and liver nonhaem iron content, whereas the brain nonhaem iron concentration still showed a significant deficit. The data thus suggest that changes in the uptake of 5-HT by brain synaptic vesicles that accompany iron depletion and repletion are more rapid than changes in the total nonhaem iron concentration in the brain. The observation that 5-HT uptake by brain synaptic vesicles is decreased in iron deficiency suggests a probable role for iron in 5-HT storage in rat brain. 相似文献
17.
Serotonin is an influential monoamine neurotransmitter that signals through a number of receptors to modulate brain function. Among different serotonin receptors, the serotonin 1A (5-HT1A) receptors have been tied to a variety of physiological and pathological processes, notably in anxiety, mood, and cognition. 5-HT1A receptors couple not only to the classical inhibitory G protein-regulated signaling pathway, but also to signaling pathways traditionally regulated by growth factors. Despite the importance of 5-HT1A receptors in brain function, little is known about how these signaling mechanisms link 5-HT1A receptors to regulation of brain physiology and behavior. Following a brief summary of the known physiological and behavioral effects of 5-HT1A receptors, this article will review the signaling pathways regulated by 5-HT1A receptors, and discuss the potential implication of these signaling pathways in 5-HT1A receptor-regulated physiological processes and behaviors. 相似文献
18.
Luiz E. A. M. Mello Zuner A. Bortolotto Esper A. Cavalheiro 《Journal of neurochemistry》1988,51(3):698-703
Previous work by other authors has shown that alloxan-induced diabetes increases whereas streptozotocin-induced diabetes does not alter nonesterified fatty acid (NEFA) plasma levels. The present study replicates these results and demonstrates that fasted, streptozotocin-induced diabetic animals also have increased NEFA levels. In addition, brain levels of 5-hydroxytryptamine (5-HT) and of its immediate precursor and metabolite were measured. Alloxan- and fasted, streptozotocin-induced diabetic rats showed significant increases in brain indoleamine concentrations, whereas fed, streptozotocin-induced diabetic rats had unchanged levels of the same compounds. Levels of brain indoleamines exhibited a strong positive correlation with wet-dog shakes (an index of 5-HT activity) elicited by hippocampal stimulation. Blockade of wet-dog shakes by 5-HT receptor antagonists strengthens the proposal that this behavior is a good index of central 5-HT activity. The increased content of brain indoleamines in alloxan- and fasted, streptozotocin-induced diabetic rats may be related to the increased NEFA plasma levels seen in the same animals. This hypothesis is supported by the positive correlation demonstrated between NEFA and 5-HT levels. In conclusion, it is suggested that alloxan-induced diabetes may represent a useful model for studying the various behavioral changes known to occur in diabetics. 相似文献
19.
5-Hydroxytryptamine (5-HT) and dopamine uptake were studied in rat hypothalamic and striatal synaptosomes, respectively, after a single-dose or repeated doses of p-chlorophenylalanine (PCPA), and after withdrawal of the drug. 5-HT uptake did not change 24 h after a single large dose of PCPA (300 mg/kg). Uptake of neither amine changed 12 h or 7 days after treatment with 300 mg/kg PCPA every third day, for 2 weeks. In all cases, the kinetic parameters remained identical. These results indicate that depletion of 5-HT levels by PCPA and the resulting decrease in serotoninergic activity do not induce changes in 5-HT or dopamine uptake. Hence, reported changes in transmitter uptake due to clinical or experimental manipulations must not be directly related to synaptic activity. 相似文献
20.
Motor effects of serotonin in the central nervous system 总被引:2,自引:0,他引:2
Serotoneric pathways in the CNS affect posture and movement, as well as behavioral responses to arousing stimuli. Pharmacologic analysis of these effects has led to an increasingly complex and confusing literature. Increased availability of serotonin (5-HT) by administration of precursors, or by its direct intracranial infusion can induce inhibitory or excitatory behavioral effects depending on the conditions of the experiment, although generally motor inhibition has been found. Availability of 5-HT has been decreased by electrolytic lesions of the raphe nuclei, inhibition of tryptophan hydroxylase, or use of selective neurotoxins. These treatments have generally increased motor activity, especially spontaneous locomotion in a familiar environment, as well as sexual or aggressive behaviors; other behaviors, such as responses in a novel environment, presumably associated with curiosity or fear, have been paradoxically decreased after loss of 5-HT. This differentiation may occur to an important extent through 5-HT projections to hippocampus and limbic structures, notably from the median raphe. Increases or decreases of brain 5-HT, respectively, generally tend to decrease and increase responses to catecholamine agonists such as amphetamines, and some effects of 5-HT may be mediated through catecholaminergic systems. Increased availability of 5-HT in the presence of MAO inhibitors, or challenge with 5-HT-agonists after selective 5-HT-denervation in the CNS has led to a behavioral syndrome marked by hyperactivity, autonomic arousal and myoclonic seizures. The mechanisms underlying this complex response may be mediated by descending 5-HT systems that result in motor excitation at the spinal cord level, in contrast to rostral projections to forebrain that may mediate many behaviorally inhibitory responses. 相似文献