The mechanism by which monoamine oxidase inhibitors give rise to a non‐calcium‐dependent component in the depolarization‐induced release of 5‐HT from rat brain synaptosomes

Evans, Susan C.; Collard, Keith J.

doi:10.1111/j.1476-5381.1988.tb11725.x

Cited by 9 publications

(6 citation statements)

References 20 publications

(32 reference statements)

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“…This functional restoration in vivo fits well with the potassium-and MDMA-induced releases of [ 3 H]5-HT observed in vitro in VMAT2 sertÀcre synaptosomes. The mechanism involved in the [ 3 H]5-HT release in VMAT2 sertÀcre synaptosomes is presently unclear, but three non-mutually exclusive possibilities can be discussed: (1) Release of [ 3 H]5-HT through the carrier (Evans and Collard, 1988). Although this was suggested to occur in VMAT2 KO mice (Fon et al, 1997), we do not presently have any data in Figure 6 The VMAT2 sertÀcre mutation decreased anxiety and locomotion but increased reactivity to stress.…”

Section: Discussionmentioning

confidence: 99%

Severe Serotonin Depletion after Conditional Deletion of the Vesicular Monoamine Transporter 2 Gene in Serotonin Neurons: Neural and Behavioral Consequences

Narboux-Nême

Sagné

Doly

et al. 2011

Neuropsychopharmacol

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The vesicular monoamine transporter type 2 gene (VMAT2) has a crucial role in the storage and synaptic release of all monoamines, including serotonin (5-HT). To evaluate the specific role of VMAT2 in 5-HT neurons, we produced a conditional ablation of VMAT2 under control of the serotonin transporter (slc6a4) promoter. VMAT2 sertÀcre mice showed a major (À95%) depletion of 5-HT levels in the brain with no major alterations in other monoamines. Raphe neurons contained no 5-HT immunoreactivity in VMAT2 sertÀcre mice but developed normal innervations, as assessed by both tryptophan hydroxylase 2 and 5-HT transporter labeling. Increased 5-HT 1A autoreceptor coupling to G protein, as assessed with agonist-stimulated [ 35 S]GTP-g-S binding, was observed in the raphe area, indicating an adaptive change to reduced 5-HT transmission. Behavioral evaluation in adult VMAT2 sertÀcre mice showed an increase in escape-like reactions in response to tail suspension and anxiolytic-like response in the novelty-suppressed feeding test. In an aversive ultrasoundinduced defense paradigm, VMAT2 sertÀcre mice displayed a major increase in escape-like behaviors. Wild-type-like defense phenotype could be rescued by replenishing intracellular 5-HT stores with chronic pargyline (a monoamine oxidase inhibitor) treatment. Pargyline also allowed some form of 5-HT release, although in reduced amounts, in synaptosomes from VMAT2 sertÀcre mouse brain. These findings are coherent with the notion that 5-HT has an important role in anxiety, and provide new insights into the role of endogenous 5-HT in defense behaviors.

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Section: Discussionmentioning

confidence: 99%

Severe Serotonin Depletion after Conditional Deletion of the Vesicular Monoamine Transporter 2 Gene in Serotonin Neurons: Neural and Behavioral Consequences

Narboux-Nême

Sagné

Doly

et al. 2011

Neuropsychopharmacol

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“…However, at present there is little evidence in support of such a view compared with that supporting the carrier-mediated theory of Nicholls (25) reviewed above. Furthermore, it has been shown that other transmitters which normally show little non-Ca2+-dependent release, can be induced, under certain experimental conditions, to release transmitters through the relevent plasma membrane carrier by a nonCa2+-dependent process (28). Whatever mechanisms may be involved, the response to short-term hypoxia in cortical synaptosomes seems to be very similar to that seen following longer exposure to hypoxic conditions (9).…”

Section: The Effect Of Hypoxia On the Release Of [3h]glutamate From Hmentioning

confidence: 91%

“…In those experiments in which the effect of removing extracellular Ca a § was examined, Ca a+ was replaced isosmotically with Na +. This procedure had been shown in previous studies to completely abolish the release of 5-[3Hlhydroxytryptamine in response to a similar depolarizing pulse of K § (28). In tissue beds which received a hypoxic insult, the tissue was perfused with standard Krebs solution, or Ca2+-free Krebs solution for 7 minutes.…”

Section: Preparation Of Synaptosomes Incubation With [3h]glutamate Amentioning

confidence: 99%

Effects of short-term hypoxia on [3H]glutamate release from preloaded hippocampal and cortical synaptosomes

Collard

Menon-Johansson

1993

Neurochem Res

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The effect of short-term hypoxia on the release of [3H]glutamate from preloaded hippocampal and cortical synaptosomes was studied in a rapid superfusion system. The technique minimised the loss of released glutamate by reuptake. The results indicated that the effects of short term hypoxia were qualitatively similar to those reported in previous studies using more long-term hypoxia, but were significantly smaller. The non-Ca(2+)-dependent efflux of glutamate from cortical synaptosomes was increased by hypoxia as was the Ca(2+)-dependent release from hippocampal tissue. Possible mechanisms for these findings were discussed. The small amplitude of these changes in comparison to the effects seen in slowly perfused tissue in vitro and in vivo indicated that the contribution made by changes in neuronal efflux to the overall increase in extracellular glutamate seen in hypoxia is relatively minor.

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“…Veratramine may act like p-chloroamphetamine or fenfluramine releasing 5-HT through a carrier-dependent mechanism (18). Recently, it has been shown that MAO inhibitors are able to increase a component of noncalcium dependent, depolarization-induced release of 3H-5-HT through the plasma membrance carrier (19). Therefore, a part of the non-calcium dependent release of 3H-5-HT evoked by veratramine may be due to the concurrent use of pargyline which was applied throughout the present release study.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of veratramine-induced 5-HT syndrome in mice.

et al. 1991

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ABSTRACT-Regional monoamine assays revealed that during veratramine-induced myoclonic movements, the contents of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in the cerebral cortex were reduced with a slight increase in dopamine metabolites in the midbrain and brainstem. A similar tendency to decrease 5-HT and 5-HIAA contents was observed in the hypothalamus and hippocampus without increase in the contents of dopamine and its metabolites. Norepinephrine levels were not modified in any brain region at any time after the administration of the veratrum alkaloid. It was found that the veratramine evoked 3H-5-HT release from the frontal cortical slices was Ca++-independent and persistent, and it continued approximately 20 min after the 2-min exposure to veratramine. The uptake of 3H-5-HT into the frontal cortical slices was inhibited competitively by veratramine. These results suggest that veratramine is both a releaser and uptake inhibitor of 5-HT and that the veratramine-induced involuntary movements may be mediated by serotonergic hyperfunction.

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The mechanism by which monoamine oxidase inhibitors give rise to a non‐calcium‐dependent component in the depolarization‐induced release of 5‐HT from rat brain synaptosomes

Cited by 9 publications

References 20 publications

Severe Serotonin Depletion after Conditional Deletion of the Vesicular Monoamine Transporter 2 Gene in Serotonin Neurons: Neural and Behavioral Consequences

Severe Serotonin Depletion after Conditional Deletion of the Vesicular Monoamine Transporter 2 Gene in Serotonin Neurons: Neural and Behavioral Consequences

Effects of short-term hypoxia on [3H]glutamate release from preloaded hippocampal and cortical synaptosomes

Mechanisms of veratramine-induced 5-HT syndrome in mice.

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