Neuropsychotoxicity of Abused Drugs: Effects of Serotonin Receptor Ligands on Methamphetamine- and Cocaine-Induced Behavioral Sensitization in Mice

Ago, Yukio; Nakamura, Shigeo; Baba, Akemichi; Matsuda, Takehisa

doi:10.1254/jphs.fm0070121

Cited by 40 publications

(30 citation statements)

References 43 publications

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“…Our present results, however, clearly indicate that acute MDMA-induced 5-HT release is due to 5-HT efflux, which was inhibited by an SSRI, being consistent with the observations in previous studies. Consistent with our study, in vivo studies have found that repeated administration of amphetamines causes augmentation of amphetamines-induced 5-HT release in the prefrontal cortex in parallel with behavioral sensitization (12,13). In contrast, it was reported that repeated administration of MDMA according to a neurotoxic regimen induced no change or reduction in 5-HT release in the hippocampus or frontal cortex in response to electrical stimulation of the dorsal or median raphe nucleus (14).…”

supporting

confidence: 89%

Sustained Exposure to 3,4-Methylenedioxymethamphetamine Induces the Augmentation of Exocytotic Serotonin Release in Rat Organotypic Raphe Slice Cultures

et al. 2010

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Abstract. 3,4-Methylenedioxymethamphetamine (MDMA) causes serotonin efflux via serotonin transporter. Recently, we have reported that sustained exposure to MDMA induced an augmentation of serotonin release in rat raphe serotonergic slice cultures. Here we investigated the mechanism of augmented serotonin release from the slice cultures. Sustained MDMA exposure had no effect on MDMA-induced serotonin efflux in the synaptosomal fraction, whereas either tetrodotoxin, calcium channel inhibitors, or AMPA-receptor antagonists significantly attenuated the augmented serotonin release. These results suggest that the increase in Ca 2+ -dependent exocytotic serotonin release is mediated through activation of AMPA receptors and responsible for the sustained MDMA-induced augmentation of serotonin release.

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supporting

confidence: 89%

Sustained Exposure to 3,4-Methylenedioxymethamphetamine Induces the Augmentation of Exocytotic Serotonin Release in Rat Organotypic Raphe Slice Cultures

et al. 2010

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“…124,130) Therefore, the results of our study imply that 5-HT 1A receptor agonists may have a therapeutic value for the treatment of METH abuse or psychosis. 131) In this relation, we also found that lithium attenuates acute METHinduced hyperactivity and chronic METH-induced behavioral sensitization via modulation of the prefrontal release of DA and 5-HT, respectively. 132) This result suggests that a 5-HT 1A receptor-mediated mechanism is involved in the effect of lithium on chronic METH-induced behavioral sensitization.…”

Section: Corticosterone Modelsupporting

confidence: 55%

Neuropharmacologic Studies on the Brain Serotonin<sub>1A</sub> Receptor Using the Selective Agonist Osemozotan

Matsuda

2013

Biological & Pharmaceutical Bulletin

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Alterations in serotonin (5-HT) neurochemistry have been implicated in the etiology of major neuropsychiatric disorders such as anxiety-spectrum disorders, depression, and schizophrenia. The neuromodulatory effects of 5-HT are mediated through 14 receptor subtypes, and those receptors, including the 5-HT 1A receptor, are considered to be potential targets for the treatment of psychiatric disorders. We developed the novel 5-HT 1A receptor agonist MKC-242 (called osemozotan) and characterized its neurochemical and pharmacological profiles. 5-HT 1A receptor agonists modulate the release of amine neurotransmitters through the activation of presynaptic or postsynaptic 5-HT 1A receptors in the brain. The agonist has antianxiety and antidepressant effects and improves abnormal behaviors such as aggressive behavior and deficits of prepulse inhibition in isolation-reared mice. We also demonstrated that spinal 5-HT 1A receptor activation is involved in isolation rearing-induced hypoalgesia. Concerning the mechanism for induction of isolation-induced abnormal behaviors, we have recently found that the raphe-prefrontal 5-HT system plays a key role in encounter stimulation-induced hyperactivity in isolation-reared mice. Furthermore, we showed that osemozotan attenuates psychostimulant-induced behavioral sensitization and that prefrontal dopamine release is enhanced by functional interaction between the 5-HT 1A receptor and other receptors. This review summarizes the neuropharmacology of the 5-HT 1A receptor, focusing on our studies using osemozotan, and suggests that the 5-HT 1A receptor may be a target molecule for the treatment of psychiatric disorders, pain, and drug dependence.

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“…The modulation of cocaine-induced behavioural sensitization by 5-HT receptor ligands has been previously observed in mice. 54 For example, 5-HT receptor antagonists [55][56][57][58] inhibit cocaine-induced behavioural sensitization, suggesting that the central 5-HT system plays an important role in this effect.…”

Section: Differential Roles Of Altered Da and 5-ht Systems On Locomotmentioning

confidence: 99%

Selective genetic disruption of dopaminergic, serotonergic and noradrenergic neurotransmission: insights into motor, emotional and addictive behaviour

Isingrini¹,

Perret²,

Rainer³

et al. 2016

jpn

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IntroductionMonoaminergic neurotransmitters, namely dopamine (DA), noradrenaline (NE) and serotonin (5-HT), extensively modulate cognitive, affective, neuroendocrine and motor functions in the brain. 1 The role of the monoaminergic systems in psychi atric pathology has been clearly established based on the observation that effective psychotropic drugs primarily target these systems. [2][3][4] However, the functional subdivision of the monoamine systems indicates a disparity in cerebral distribution, receptor subtypes and mechanisms of action. Unravelling the independent roles of the monoaminergic systems in patients with neuropsychiatric disorders remains a challenge that is complicated by their large anatomic, pharmacological and functional overlaps.At the molecular level, the monoaminergic systems share common properties. The intra-and extracellular concentrations of monoamines are primarily controlled by 2 types of transporters. The plasma membrane transporters (norepinephrine transporter [NET], serotonin transporter [SERT] and dopamine transporter [DAT]) play an essential role in the clearance and recycling of monoamines via uptake from the extracellular space, and the vesicular monoamine transporter (VMAT) accumulates monoamines in synaptic vesicles and is essential for their release. 5 Two VMAT genes have been cloned, 6,7 and although the proteins encoded by these genes are structurally related, they fulfill distinct roles. VMAT1 is primarily expressed in the peripheral nervous system; VMAT2 is primarily expressed in the neurons of the central nervous system. 8,9 The functions of VMAT2 include storage of monoamines, protection of monoamines from cytoplasmic oxi dation and regulation of stimulated monoamine quantal release. 10 Thus, VMAT2 deficiency contributes to a decrease in the synaptic release of monoamines and an increase in the degradation of intracellular monoamines.To better understand the physiologic and behavioural roles of monoaminergic signalling, several investigators have created VMAT2-knockout (KO) mice by disrupting the gene that Background:The monoaminergic transmitters dopamine (DA), noradrenaline (NE) and serotonin (5-HT) modulate cerebral functions via their extensive effects in the brain. Investigating their roles has led to the creation of vesicular monoaminergic transporter-2 (VMAT2) knockout (KO) mice. While this mutation results in postnatal death, VMAT2-heterozygous (HET) mice are viable and show a complex behavioural phenotype. However, the simultaneous alteration of the 3 systems prevents investigations into their individual functions. Methods: To assess the specific role of NE, 5-HT and DA, we genetically disrupted their neurotransmission by creating conditional VMAT2-KO mice with targeted recombination. These specific recombinations were obtained by breeding VMAT2 lox/lox mice with DBHcre, SERTcre and DATcre mice, respectively. We conducted a complete neurochemical and behavioural characterization of VMAT2-HET animals in each system. Results: Conditional VMAT2-KO mice reveale...

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Neuropsychotoxicity of Abused Drugs: Effects of Serotonin Receptor Ligands on Methamphetamine- and Cocaine-Induced Behavioral Sensitization in Mice

Cited by 40 publications

References 43 publications

Sustained Exposure to 3,4-Methylenedioxymethamphetamine Induces the Augmentation of Exocytotic Serotonin Release in Rat Organotypic Raphe Slice Cultures

Sustained Exposure to 3,4-Methylenedioxymethamphetamine Induces the Augmentation of Exocytotic Serotonin Release in Rat Organotypic Raphe Slice Cultures

Neuropharmacologic Studies on the Brain Serotonin<sub>1A</sub> Receptor Using the Selective Agonist Osemozotan

Selective genetic disruption of dopaminergic, serotonergic and noradrenergic neurotransmission: insights into motor, emotional and addictive behaviour

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