Effects of repeated systemic administration of d -Fenfluramine on serotonin and glutamate release in rat ventral hippocampus: comparison with methamphetamine using in vivo microdialysis

Rocher, Cyril; Am, Gardier

doi:10.1007/s002100000381

Cited by 50 publications

(12 citation statements)

References 29 publications

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“…Adult and adolescent rats were injected with either saline or fenfluramine (2 mg/kg) 30 minutes prior to testing (n=12 per age, per treatment). This dose of fenfluramine was expected to be non-maximal in terms of increasing extracellular serotonin in the brain (Gundlah et al, 1997; Rocher and Gardier, 2001; Tao et al, 2002). For each age group, saline-treated animals were used as a control group to determine baseline behavior.…”

Section: Methodsmentioning

confidence: 99%

Adolescent male rats are less sensitive than adults to the anxiogenic and serotonin-releasing effects of fenfluramine

2013

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Risk taking behavior increases during adolescence, which is also a critical period for the onset of drug abuse. The central serotonergic system matures during the adolescent period, and its immaturity during early adolescence may contribute to adolescent risk taking, as deficits in central serotonergic function have been associated with impulsivity, aggression, and risk taking. We investigated serotonergic modulation of behavior and presynaptic serotonergic function in adult (67–74 days old) and adolescent (28–34 days old) male rats. Fenfluramine (2 mg/kg, i.p.) produced greater anxiogenic effects in adult rats in both the light/dark and elevated plus maze tests for anxiety-like behavior, and stimulated greater increases in extracellular serotonin in the adult medial prefrontal cortex (mPFC) (1, 2.5, and 10 mg/kg, i.p.). Local infusion of 100 mM potassium chloride into the mPFC also stimulated greater serotonin efflux in adult rats. Adult rats had higher tissue serotonin content than adolescents in the prefrontal cortex, amygdala, and hippocampus, but the rate of serotonin synthesis was similar between age groups. Serotonin transporter (SERT) immunoreactivity and SERT radioligand binding were comparable between age groups in all three brain regions. These data suggest that lower tissue serotonin stores in adolescents limit fenfluramine-stimulated serotonin release and so contribute to the lesser anxiogenic effects of fenfluramine.

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Section: Methodsmentioning

confidence: 99%

Adolescent male rats are less sensitive than adults to the anxiogenic and serotonin-releasing effects of fenfluramine

2013

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“…In addition to increases in both DA and 5HT, amphetamine-related drugs of abuse also increase extracellular levels of glutamate in both the striatum and hippocampus (Rocher and Gardier 2001; Nash and Yamamoto 1992; Cunningham et al 2004). Despite the actions of METH and MDMA at DAT and SERT, there is no indication that increases in glutamate are mediated by a direct interaction with the plasmalemmal glutamate transporter (Kokoshka et al 1998).…”

Section: Basic Neuropharmacology Of Meth and Mdmamentioning

confidence: 99%

The Role of Oxidative Stress, Metabolic Compromise, and Inflammation in Neuronal Injury Produced by Amphetamine-Related Drugs of Abuse

Yamamoto

Raudensky

2008

J Neuroimmune Pharmacol

142

111

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Methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) are amphetamine derivatives with high abuse liability. These amphetamine-related drugs of abuse mediate their effects through the acute activation of both dopaminergic and serotonergic neurons. Long-term abuse of these amphetamine derivatives, however, results in damage to both dopaminergic and serotonergic terminals throughout the brain. This toxicity is mediated in part by oxidative stress, metabolic compromise, and inflammation. The overall objective of this review is to highlight experimental evidence that METH and MDMA increase oxidative stress, produce mitochondrial dysfunction, and increase inflammation that converge and culminate in the long-term toxicity to dopaminergic and serotonergic neurons.

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“…It has been shown that repeated high dose treatment with MA (10 mg/kg every 2 hrs × 4) can lead to damage of dopaminergic terminals and increases of extracellular glutamate concentration (Thomas et al, 2004; Halpin et al, 2013; Bowyer et al, 1994). In addition, studies reported that repeated MA exposure can lead to increase in both extracellular concentrations of dopamine and glutamate in the striatum (Nash and Yamamoto, 1992) and hippocampus (Rocher and Gardier, 2001). Although, it is now well known about the effects of MA exposure in the increase of extracellular glutamate in specific brain regions, there is little known about its effects on glutamate transporters after MA administration or MA administered sequentially with EtOH.…”

Section: Introductionmentioning

confidence: 99%

Effects of Administered Ethanol and Methamphetamine on Glial Glutamate Transporters in Rat Striatum and Hippocampus

2016

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Exposure to ethanol (EtOH) or methamphetamine (MA) can lead to increase in extracellular glutamate concentration in the brain. Although studies from ours showed the effects of EtOH exposure on key glial glutamate transporters, there is less known about the effects of sequential exposure to EtOH and MA or MA alone on certain glial glutamate transporters. In this study, we investigated the effects of sequential exposure to EtOH and MA on the expression of the major glutamate transporter, glutamate transporter 1 (GLT-1), as well as cystine/glutamate antiporter (xCT) and glutamate aspartate transporter (GLAST) in striatum and hippocampus. We also tested the effects of ceftriaxone (CEF), known to upregulate GLT-1, in animals administered EtOH and MA. Wistar rats were orally gavaged with EtOH (6 g/kg) or water for seven days. On the following day (Day 8), rats received four intraperitoneal (i.p.) injections of MA (10 mg/kg) or saline (vehicle) occurring every 2 hours. Rats were then treated with CEF (200 mg/kg/day, i.p.) or saline on Day 8, 9 and 10. EtOH or MA exposure caused a significant downregulation of GLT-1 expression as compared to control groups in striatum and hippocampus. Furthermore, sequential exposure of EtOH and MA caused a significant downregulation of GLT-1 expression as compared to either drug administered alone in both brain regions. Importantly, GLT-1 expression was restored following CEF treatment. These findings demonstrated that sequential exposure to EtOH and MA has synergistic effect in downregulation of GLT-1 and this effect can be attenuated by CEF treatment.

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Effects of repeated systemic administration of d -Fenfluramine on serotonin and glutamate release in rat ventral hippocampus: comparison with methamphetamine using in vivo microdialysis

Cited by 50 publications

References 29 publications

Adolescent male rats are less sensitive than adults to the anxiogenic and serotonin-releasing effects of fenfluramine

Adolescent male rats are less sensitive than adults to the anxiogenic and serotonin-releasing effects of fenfluramine

The Role of Oxidative Stress, Metabolic Compromise, and Inflammation in Neuronal Injury Produced by Amphetamine-Related Drugs of Abuse

Effects of Administered Ethanol and Methamphetamine on Glial Glutamate Transporters in Rat Striatum and Hippocampus

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