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1.
The nucleus accumbens is believed to play a critical role in mediating the behavioral responses to rewarding stimuli. Although most studies of the accumbens focus on dopamine, it receives afferents from many other nuclei, including noradrenergic cell groups in the brainstem. We used in vivo microdialysis to measure extracellular levels of both norepinephrine and dopamine in the accumbens shell and core. Regional analysis of shell and core and border regions demonstrated that norepinephrine was high in shell and decreased from medial shell to lateral core, where baseline levels were low or undetectable. Conversely, extracellular dopamine in core was twice the level seen in shell. Both catecholamines increased following a single injection of amphetamine (2 mg/kg, i.p.). The norepinephrine response was greater and long-lasting in shell compared with core. The maximal dopamine response was higher in core than in shell, but the duration of the effect was comparable in both regions. The distinct neurochemical characteristics of shell and core are likely to contribute to the functional heterogeneity of the two subregions. Furthermore, norepinephrine may be involved in many of the functions generally attributed to the accumbens, either directly or indirectly via modulation of extracellular dopamine. 相似文献
2.
Amphetamine is more effective than methamphetamine at raising dopamine levels in the prefrontal cortex. The current study tested the hypothesis that norepinephrine transporters are involved in this difference. Using microdialysis, dopamine, norepinephrine, and serotonin were measured in the rat prefrontal cortex after administration of methamphetamine or amphetamine, with and without perfusion of desipramine. Amphetamine raised norepinephrine levels more than methamphetamine did. Desipramine raised dopamine and serotonin levels but did not alter metabolite levels. Desipramine attenuated the increase in dopamine by amphetamine while increasing the dopamine released by methamphetamine. These data suggest that methamphetamine and amphetamine differ in altering prefrontal cortical dopamine levels and in interacting with norepinephrine transporters. It is proposed that amphetamine releases dopamine in the prefrontal cortex primarily through norepinephrine transporters, whereas methamphetamine interacts minimally with norepinephrine transporters. 相似文献
3.
Kleijn J Wiskerke J Cremers TI Schoffelmeer AN Westerink BH Pattij T 《Neurochemistry international》2012,60(8):791-798
The psychostimulant drug amphetamine is often prescribed to treat Attention-Deficit/Hyperactivity Disorder. The behavioral effects of the psychostimulant drug amphetamine depend on its ability to increase monoamine neurotransmission in brain regions such as the nucleus accumbens (NAC) and medial prefrontal cortex (mPFC). Recent behavioral data suggest that the endocannabinoid system also plays a role in this respect. Here we investigated the role of cannabinoid CB1 receptor activity in amphetamine-induced monoamine release in the NAC and/or mPFC of rats using in vivo microdialysis. Results show that systemic administration of a low, clinically relevant dose of amphetamine (0.5mg/kg) robustly increased dopamine and norepinephrine release (to ~175-350% of baseline values) in the NAC shell and core subregions as well as the ventral and dorsal parts of the mPFC, while moderately enhancing extracellular serotonin levels (to ~135% of baseline value) in the NAC core only. Although systemic administration of the CB1 receptor antagonist SR141716A (0-3mg/kg) alone did not affect monoamine release, it dose-dependently abolished amphetamine-induced dopamine release specifically in the NAC shell. SR141716A did not affect amphetamine-induced norepinephrine or serotonin release in any of the brain regions investigated. Thus, the effects of acute CB1 receptor blockade on amphetamine-induced monoamine transmission were restricted to dopamine, and more specifically to mesolimbic dopamine projections into the NAC shell. This brain region- and monoamine-selective role of CB1 receptors is suggested to subserve the behavioral effects of amphetamine. 相似文献
4.
两侧对称动物左右体轴建立机制研究是发育生物学领域重要的基础科学问题之一。文昌鱼(amphioxus)由于其特殊的进化地位以及与脊椎动物相似的胚胎发育模式和身体构筑方式,是研究动物左右体轴建立机制的理想模式物种。近年来随着文昌鱼室内全人工繁育技术、高效显微注射技术和基因敲除技术的建立,国内外学者在左右体轴建立机制研究上取得了丰硕的成果。本文从文昌鱼胚胎左右不对称发育特点出发,总结了近期文昌鱼左右体轴建立方面取得的研究进展,并提出了文昌鱼左右体轴调控网络图:纤毛运动导致Hh蛋白在文昌鱼中不对称分布(L相似文献
5.
The Prefrontal Cortex Regulates the Basal Release of Dopamine in the Limbic Striatum: An Effect Mediated by Ventral Tegmental Area 总被引:9,自引:2,他引:7
Abstract: The present study examined whether the prefrontal cortex (PFC) exerts a tonic control over the basal release of dopamine in the limbic striatum and whether this control is mediated by glutamatergic afferents to the dopamine cell body or terminal regions. Using intracerebral microdialysis in freely moving rats, it was demonstrated that application of tetrodotoxin in the contralateral PFC significantly decreased the release of dopamine in the medial striatum. Conversely, blockade of the tonic inhibitory GABAergic input in the PFC with bicuculline increased the release of dopamine in the medial striatum. Application of excitatory amino acid receptor antagonists into the striatum, while bicuculline was perfused in the PFC, did not affect the bicuculline-evoked dopamine increase in the striatum. However, infusion of tetrodotoxin or excitatory amino acid receptor antagonists into the ventral tegmental area, a region containing dopamine cell bodies that project to the medial striatum, blocked the stimulation of striatal dopamine release induced by infusion of bicuculline into the PFC. These data demonstrate that the basal output of dopamine terminals in the medial striatum is under a tonic excitatory control of the PFC. Furthermore, this control occurs primarily through glutamatergic projections to the dopamine cell body area rather than the terminal regions. 相似文献
6.
Effects of Methylphenidate on Extracellular Dopamine, Serotonin, and Norepinephrine: Comparison with Amphetamine 总被引:18,自引:2,他引:16
Abstract: Methylphenidate promotes a dose-dependent behavioral profile that is very comparable to that of amphetamine. Amphetamine increases extracellular norepinephrine and serotonin, in addition to its effects on dopamine, and these latter effects may play a role in the behavioral effects of amphetamine-like stimulants. To examine further the relative roles of dopamine, norepinephrine, and serotonin in the behavioral response to amphetamine-like stimulants, we assessed extracellular dopamine and serotonin in caudate putamen and norepinephrine in hippocampus in response to various doses of methylphenidate (10, 20, and 30 mg/kg) that produce stereotyped behaviors, and compared the results with those of a dose of amphetamine (2.5 mg/kg) that produces a level of stereotypies comparable to the intermediate dose of methylphenidate. The methylphenidate-induced changes in dopamine and its metabolites were consistent with changes induced by other uptake blockers, and the magnitude of the dopamine response for a behaviorally comparable dose was considerably less than that with amphetamine. Likewise, the dose-dependent increase in norepinephrine in response to methylphenidate was also significantly less than that with amphetamine. However, in contrast to amphetamine, methylphenidate had no effect on extracellular serotonin. These results do not support the hypothesis that a stimulant-induced increase in serotonin is necessary for the appearance of stereotyped behaviors. 相似文献
7.
Brain norepinephrine and dopamine regulate a variety of critical behaviors such as stress, learning, memory, and drug addiction. In this study, we demonstrate differences in the regulation of in vivo neurotransmission for dopamine in the anterior nucleus accumbens (NAc) and norepinephrine in the ventral bed nucleus of the stria terminalis (vBNST) of the anesthetized rat. Release of the two catecholamines was measured simultaneously using fast-scan cyclic voltammetry at two different carbon-fiber microelectrodes, each implanted in the brain region of interest. Simultaneous dopamine and norepinephrine release was evoked by electrical stimulation of a region where the ventral noradrenergic bundle, the pathway of noradrenergic neurons, courses through the ventral tegmental area/substantia nigra, the origin of dopaminergic cell bodies. The release and uptake of norepinephrine in the vBNST were both significantly slower than for dopamine in the NAc. Pharmacological manipulations in the same animal demonstrated that the two catecholamines are differently regulated. The combination of a dopamine autoreceptor antagonist and amphetamine significantly increased basal extracellular dopamine whereas a norepinephrine autoreceptor antagonist and amphetamine did not change basal norepinephrine concentration. α-Methyl-p-tyrosine, a tyrosine hydroxylase inhibitor, decreased electrically evoked dopamine release faster than norepinephrine. The dual-microelectrode fast-scan cyclic voltammetry technique along with anatomical and pharmacological evidence confirms that dopamine in the NAc and norepinephrine in the vBNST can be monitored selectively and simultaneously in the same animal. The high temporal and spatial resolution of the technique enabled us to examine differences in the dynamics of extracellular norepinephrine and dopamine concurrently in two different limbic structures. 相似文献
8.
M. H. Meshki Baf M. N. Subhash K. Madepalli Lakshmana B. S. Sridhara Rama Rao 《Neurochemical research》1994,19(9):1139-1143
Carbamazepine (25 mg/kg body weight) was administered intraperitoneally to adult male Wistar rats for 45 days and norepinephrine (NE), dopamine (DA) and serotonin (5-HT) levels were simultaneously assayed in discrete brain regions by high performance liquid chromatographic (HPLC) method. Experimental rats displayed no behavioral abnormalities. Body and brain weights were not significantly different from control group of rats. After exposure it was observed that norepinephrine levels were elevated in motor cortex (P<0.01) and cerebellum (P<0.05), while dopamine levels were decreased in these two regions (P<0.001, P<0.05). However, dopamine levels were increased in hippocampus (P<0.01). Serotonin levels were significantly decreased in motor cortex (P<0.001) and hypothalamus (P<0.001) but increased in striatum-accumbens (P<0.001) and brainstem (P<0.001). These results suggest that carbamazepine may mediate its anticonvulsant effect by differential alterations of monoamine levels in discrete brain regions particularly in motor cortex and cerebellum. 相似文献
9.
In Vivo Dynamics of Norepinephrine Release-Reuptake in Multiple Terminal Field Regions of Rat Brain 总被引:1,自引:0,他引:1
Abstract: Electrical stimulation of the ascending dorsal tegmental bundle of the locus ceruleus was used to elicit controlled release of norepinephrine. Real-time in vivo monitoring in the brains of urethane-anesthetized rats was observed with high speed chronocoulometry at rapidly responding carbon fiber electrodes. Using modeling similar to that developed for dopamine release, the electrochemical signals were characterized as the balance between norepinephrine release per electrical stimulation pulse and apparent Michaelis-Menten reuptake parameters. Stimulation produced simultaneous overflow release at all terminal fields examined. The release and reuptake characteristics varied considerably in different regions. If the parameters are normalized to endogenous concentration in the terminal fields, release but not reuptake correlates with innervation density in several regions. Stimulated release results in norepinephrine overflow and transport in most brain regions with half-lives of 1–3 s and overflow distances of 25–50 µm at most. A surprising exception occurs in the upper layers of cortex (cingulate and sensory) where half-lives may be in the 10s of seconds and spatial reach may be up to 100 µm. The uptake in the outer cortical layers appears to be minimal and comparable with only nonspecific reuptake. 相似文献
10.
Yukio Ago Masato Umehara Kosuke Higashino Shigeru Hasebe Kazumi Fujita Kazuhiro Takuma Toshio Matsuda 《Neurochemical research》2014,39(5):825-832
Spontaneously hypertensive rats (SHRs) are used as a model for attention-deficit/hyperactivity disorder (ADHD), since SHRs are hyperactive and show defective sustained attention in behavioral tasks. The psychostimulants amphetamine and methylphenidate and the selective norepinephrine reuptake inhibitor atomoxetine are used as ADHD medications. The effects of high K+ stimulation or psychostimulants on brain norepinephrine or dopamine release in SHRs have been previously studied both in vitro and in vivo, but the effects of atomoxetine on these neurotransmitters have not. The present study examined the effects of administration of atomoxetine on extracellular norepinephrine, dopamine, and serotonin levels in the prefrontal cortex of juvenile SHRs and Wistar-Kyoto (WKY) rats. Baseline levels of prefrontal norepinephrine, dopamine, and serotonin were similar in SHRs and WKY rats. Systemic administration of atomoxetine (3 mg/kg) induced similar increases in prefrontal norepinephrine and dopamine, but not serotonin, levels in both strains. Furthermore, there was no difference in high K+-induced increases in extracellular norepinephrine, dopamine, and serotonin levels in the prefrontal cortex between SHRs and WKY rats. These findings indicate that monoamine systems in the prefrontal cortex are similar between SHRs and WKY rats. 相似文献
11.
Effects of Daily Cocaine and Morphine Treatment on Somatodendritic and Terminal Field Dopamine Release 总被引:3,自引:2,他引:1
Daily injections of cocaine or morphine into rodents produces behavioral sensitization such that the last daily injection results in a greater motor stimulant effect than the first injection. To evaluate a role for brain dopamine in behavioral sensitization to cocaine and morphine, tissue slices from the ventromedial mesencephalon (containing dopamine cell bodies), the nucleus accumbens, and striatum (dopamine terminal fields) were obtained from rats pretreated with daily cocaine, morphine, or saline 2-3 weeks earlier. When the tissue slices were depolarized by increasing potassium concentration in the superfusate, the release of endogenous dopamine from the ventromedial mesencephalon of cocaine- and morphine-pretreated rats was significantly decreased. In contrast, the release of dopamine from the nucleus accumbens and striatum was either unaltered or slightly enhanced in rats pretreated with cocaine and morphine. When dopamine was released by amphetamine, a significant decrease in dopamine release from the ventromedial mesencephalon of cocaine-pretreated rats was measured. No other significant changes were measured after amphetamine-induced release. It is postulated that the decrease in dopamine release from the ventromedial mesencephalon of cocaine- and morphine-sensitized rats results in less somatodendritic autoreceptor stimulation, and thereby produces an increase in dopamine neuronal activity. 相似文献
12.
Norepinephrine Depletion in the Spinal Cord Gray Matter of Rats with Experimental Allergic Encephalomyelitis 总被引:1,自引:1,他引:0
Norepinephrine and dopamine concentrations were determined by radioenzymatic assay in discrete gray matter regions of the spinal cords of rats with experimental allergic encephalomyelitis (EAE). Norepinephrine was depleted in most spinal cord regions of EAE rats compared with controls, whereas dopamine depletion in EAE rats was restricted to the cervical dorsal horn. There was a rostrocaudal gradient of norepinephrine reduction in the spinal cords of the EAE rats with most severe depletion in the lumbar region. The results of this experiment confirmed recent anatomical observations that suggested that catecholamine-fluorescent axons and terminals were damaged in spinal cords of rats with EAE. 相似文献
13.
Differences of behavior in rats have been noted when using d-amphetamine or β-phenylethylamine (PEA). Both these drugs can disaggregate polyribosomes. It would appear that amphetamine affects both behavior and polyribosomal disaggregation through the release and activity of dopamine, while PEA acts through serotonin and to a lesser degree through norepinephrine and dopamine. 相似文献
14.
Amphetamine has well‐established actions on pre‐synaptic dopamine signaling, such as inhibiting uptake and degradation, activating synthesis, depleting vesicular stores, and promoting dopamine‐transporter reversal and non‐exocytotic release. Recent in vivo studies have identified an additional mechanism: augmenting vesicular release. In this study, we investigated how amphetamine elicits this effect. Our hypothesis was that amphetamine enhances vesicular dopamine release in dorsal and ventral striata by differentially targeting dopamine synthesis and degradation. In urethane‐anesthetized rats, we employed voltammetry to monitor dopamine, electrical stimulation to deplete stores or assess vesicular release and uptake, and pharmacology to isolate degradation and synthesis. While amphetamine increased electrically evoked dopamine levels, inhibited uptake, and up‐regulated vesicular release in both striatal sub‐regions in controls, this psychostimulant elicited region‐specific effects on evoked levels and vesicular release but not uptake in drug treatments. Evoked levels better correlated with vesicular release compared with uptake, supporting enhanced vesicular release as an important amphetamine mechanism. Taken together, these results suggested that amphetamine enhances vesicular release in the dorsal striatum by activating dopamine synthesis and inhibiting dopamine degradation, but targeting an alternative mechanism in the ventral striatum. Region‐distinct activation of vesicular dopamine release highlights complex cellular actions of amphetamine and may have implications for its behavioral effects. 相似文献
15.
Beginning on the fifth day of gestation, rats were administered 1 or 3 mg/kg of -amphetamine sulfate s.c. twice daily until term. The administration of -amphetamine caused a dose-related increase in pup mortality. However, the increase in pup death could not be correlated with any gross pathological signs. The surviving 3 mg/kg amphetamine pups were analyzed for changes in motor behavior and brain biogenic amine levels. It was found that the amphetamine offspring showed a marked reduction in the ability to habituate to new surroundings, and this effect persisted for at least three months after birth. On day 35, brain levels of norepinephrine in the “amphetamine” offspring were decreased 21 percent. On day 84, in the “amphetamine offspring,” norepinephrine levels were reduced 18 percent in both the diencephalon and brainstem; dopamine levels were reduced 21 percent in the brainstem compared to control offspring. 相似文献
16.
Concentrations of 3,4-Dihydroxyphenylalanine and Catecholamines and Metabolites in Brain in an Anhepatic Model of Hepatic Encephalopathy 总被引:2,自引:0,他引:2
Robert Hadesman Russell H. Wiesner V. L. W. Go Gertrude M. Tyce 《Journal of neurochemistry》1995,65(3):1166-1175
Abstract: Alterations in the catecholaminergic neurotransmitter systems have been shown to occur in hepatic failure and may contribute to development of hepatic encephalopathy. In the present study we used the rat after complete hepatectomy as a model for study of changes that occur in brain in acute liver failure. We attempted to identify processes in the synthesis, storage, and metabolism of catecholamine neurotransmitters that might be changed during liver failure by measuring levels of, together with those of norepinephrine and dopamine, the precursor (3,4-dihydroxyphenylalanine) and the neuronal metabolites of dopamine and norepinephrine (3,4-dihydroxyphenylacetic acid and 3,4-dihydroxyphenylglycol, respectively) in different regions of brains of control rats and of rats after hepatectomy. We found that in most brain regions of hepatectomized rats there were increases in the concentration of 3,4-dihydroxyphenylalanine or of dopamine but decreases in the concentrations of norepinephrine or of 3,4-dihydroxyphenylglycol. The particulate/supernatant ratios of catecholamines are indices of retention of neurotransmitters in storage sites. These ratios were not different in brain regions between control rats and hepatectomized rats, suggesting that vesicular retention of catecholamines in brain was not impaired after hepatectomy. The data suggest that inhibition of dopamine-β-hydroxylase might be a characteristic of hepatic failure. 相似文献
17.
L Kh Allikmets 《Zhurnal vysshe? nervno? deiatelnosti imeni I P Pavlova》1975,25(1):164-170
The effect of serotoninergic (serotonin, 1-trytophane, imipramime, methysergide), catecholaminergic (noradrenaline, amphetamine, dopamine, 1-DOPA, iproniazid) and cholinergic drugs (physostigmine, atropine, benactyzine) on emotional reactions and orienting-motor activity, as well as the effect of these drugs on shock-elicited aggressiveness enhanced by intraamygdaloid microinjection of acetylcholine was investigated in experiments on amygdalectomized male albino rats. In amygdalectomized animals, as compared to control false-operated rats, the stimulating effect of amphetamine, imipramine, tryptophane and m-cholinoblockators was enhanced and their inhibitory effect was weakened. Bilateral microinjection of cholinergic drugs (acetylcholine, physostigmine and carbacholine) and noradrenaline into the amygdaloid body intensified emotional reactivity and aggressiveness. Microinjection of serotonin and dopamine inhibited aggressiveness and caused facilitaion of orienting-motor activity. It is suggested that the adrenergic system intensifies and serotoninergic system depresses the m-cholinergic trigger mechanism of aggressive behavior in limbico-diencephalic structures. 相似文献
18.
Biochemistry of Somatodendritic Dopamine Release in Substantia Nigra: An In Vivo Comparison with Striatal Dopamine Release 总被引:11,自引:5,他引:6
Abstract: The somatodendritic release of dopamine in substantia nigra previously has been suggested to be nonvesicular in nature and thus to differ from the classical, exocytotic release of dopamine described for the dopaminergic nerve terminal in striatum. We have compared the effects of reserpine, a compound that disrupts vesicular sequestration of monoamines, on the storage and release of dopamine in substantia nigra and striatum of rats. Reserpine administration (5 mg/kg, i.p.) significantly decreased the tissue level of dopamine in substantia nigra pars reticulata, substantia nigra pars compacta, and striatum. In these brain areas, reserpine-induced reductions in tissue dopamine level occurred within 2 h and persisted at 24 h postdrug. In vivo measurements using microdialysis revealed that reserpine administration rapidly decreased the extracellular dopamine concentration to nondetectable levels in substantia nigra as well as in striatum. In both structures, it was observed that reserpine treatment significantly attenuated the release of dopamine evoked by a high dose of amphetamine (10 mg/kg, i.p.) given 2 h later. In contrast, dopamine efflux in response to a low dose of amphetamine (2 mg/kg, i.p.) was not altered by reserpine pretreatment either in substantia nigra or in striatum. The present data suggest the existence, both at the somatodendritic and at the nerve terminal level, of a vesicular pool of dopamine that is the primary site of transmitter storage and that can be displaced by high but not low doses of amphetamine. The physiological release of dopamine in substantia nigra and in striatum is dependent on the integrity of this vesicular store. 相似文献
19.
The levels of dopamine (DA) was determined by intracerebral microdialysis in vivo in KM rats selected for high audiogenic epilepsy, and in Wistar rats selected for nonsusceptibility to loud sound. The basal level of dopamine was 25% higher in the KM rats (P < 0.05). A single amphetamine injection (1 mg/kg body weight, intraperitoneously) caused a significant increase in the DA basal level up to 250-260% in animals of both genotypes. However, in Wistar rats, the level of DA reached maximum as soon as 20 min after amphetamine administration, whereas in KM rats, this happened only after 120 min. After a single injection of the antagonist of D2 and D3 dopamine receptors raclopride (1.2 mg/kg of body weight, intraperitoneously), an increase in the level of DA was similar in amplitude in rats of both genotypes (up to about 210%); however, this occurred 20-30 and 100 min after raclopride administration to Wistar and KM rats, respectively. This evidence suggests that the genetic defect of KM rats, namely, the high level of audiogenic epilepsy, is caused by abnormalities of the neuromediator brain systems and presumably accompanied by the regulatory gene dysfunction. 相似文献
20.
Owens WA Sevak RJ Galici R Chang X Javors MA Galli A France CP Daws LC 《Journal of neurochemistry》2005,94(5):1402-1410
Insulin affects brain reward pathways and there is converging evidence that this occurs through insulin regulation of the dopamine (DA) transporter (DAT). In rats made hypoinsulinemic by fasting, synaptosomal DA uptake is reduced. Interestingly, [3H]DA uptake is increased in hypoinsulinemic rats with a history of amphetamine self-administration. The possibility that amphetamine and insulin act in concert to regulate DAT activity prompted this study. Here we show that [3H]DA uptake, measured in vitro and clearance of exogenously applied DA in vivo, is significantly reduced in rats made hypoinsulinemic by a single injection of streptozotocin. Strikingly, amphetamine (1.78 mg/kg, given every other day for 8 days) restored DA clearance in streptozotocin-treated rats but was without effect on DA clearance in saline-treated rats. Basal locomotor activity of streptozotocin-treated rats was lower compared to control rats; however, in streptozotocin-treated rats, hyperlocomotion induced by amphetamine increased over successive amphetamine injections. In saline-treated rats the locomotor stimulant effect of amphetamine remained stable across the four amphetamine injections. These results provide exciting new evidence that actions of amphetamine on DA neurotransmission are insulin-dependent and further suggest that exposure to amphetamine may cause long-lasting changes in DAT function. 相似文献