Activation of GABA‐B receptors induced by systemic amphetamine abolishes dopamine release in the rat lateral septum

Sotomayor‐Zárate, Ramón; Araya, Katherine A.; Pereira, Paulo; Blanco, Edgar E.; Quiroz, Gabriel; Pozo, Sergio; Carreño, Paz; Andrés, Marı́a Estela; Forray, María Inés; Gysling, Katia

doi:10.1111/j.1471-4159.2010.06877.x

Cited by 25 publications

(19 citation statements)

References 41 publications

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“…HPLC‐Electrochemical determination of DA was performed as described previously . Briefly, 10 μL of dialysates was injected into an HPLC system with the following configuration: an isocratic pump (model PU‐2080 Plus, Jasco Co. Ltd., Tokyo, Japan), a UniJet microbore column (MF‐8949, BAS, West Lafayette, IN, USA) and an amperometric detector set at 650 mV and 0.5 nA (model LC‐4C, BAS).…”

Section: Methodsmentioning

confidence: 99%

4‐Methylthioamphetamine Increases Dopamine in the Rat Striatum and has Rewarding Effects In Vivo

Sotomayor‐Zárate

Quiroz

Araya

et al. 2012

Basic Clin Pharma Tox

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4-Methylthioamphetamine (MTA) is a phenylisopropylamine derivative whose use has been associated with severe intoxications. MTA is usually regarded as a selective serotonin-releasing agent. Nevertheless, previous data have suggested that its mechanism of action probably involves a catecholaminergic component. As little is known about dopaminergic effects of this drug, in this work the actions of MTA upon the dopamine (DA) transporter (DAT) were studied in vitro, in vivo and in silico. Also, the possible abuse liability of MTA was behaviourally assessed. MTA exhibited an in vitro affinity for the rat DAT in the low micromolar range (6.01 lM) and induced a significant, dose-dependent increase in striatal DA. MTA significantly increased c-Fos-positive cells in striatum and nucleus accumbens, induced conditioned place preference and increased locomotor activity. Docking experiments were performed in a homology model of the DAT. In conclusion, our results show that MTA is able to increase extracellular striatal DA levels and that its administration has rewarding properties. These effects were observed at concentrations or doses that can be relevant to its use in human beings.4-Methylthioamphetamine (MTA) is a phenylisopropylamine derivative originally synthesized and evaluated as an anorectic drug more than 40 years ago [1]. Subsequently, it was demonstrated that MTA is a potent, selective and non-neurotoxic serotonin (5-HT)-releasing agent in vitro [2,3] and in vivo [4], an effect that is mediated via the 5-HT transporter (SERT) [5,6]. MTA gained notoriety in the late 1990s as a street drug commonly known as 'flatliner', and its use has been associated with severe intoxications and several deaths [7][8][9][10]. Even though MTA is usually regarded as a selective serotonergic agent, it also potently inhibits monoamine oxidase-A (MAO-A) [4,11], and both hyperthermia [12] and aortic contraction [13] induced by MTA in rodent models can be blocked by a-adrenergic antagonists. In addition, it has been shown that MTA induces dopamine (DA) release from rat striatal synaptosomes pre-loaded with [ 3

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Section: Methodsmentioning

confidence: 99%

4‐Methylthioamphetamine Increases Dopamine in the Rat Striatum and has Rewarding Effects In Vivo

Sotomayor‐Zárate

Quiroz

Araya

et al. 2012

Basic Clin Pharma Tox

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“…ADHD medication increases GABA in animal models (Freese et al, 2012, Goitia et al, 2013, Sotomayor-Zárate et al, 2010) and Bollmann et al (Bollmann et al, 2015) have demonstrated that age is a factor that needs to be considered as the GABAergic system continues to develop throughout childhood and adolescence (Andersen, 2003, Luján et al, 2005). Hence, an aberration from the normal development of the GABAergic system could result in a later imbalance between excitatory and inhibitory neurotransmission, that could play a role in the pathophysiology and persistence of ADHD (Ferreira et al, 2009, Luján et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Age-dependent, lasting effects of methylphenidate on the GABAergic system of ADHD patients

Solleveld

Schrantee

Puts³

et al. 2017

NeuroImage: Clinical

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Stimulants are the main pharmacological treatment for patients with attention-deficit/hyperactivity disorder (ADHD). Their current prescription rates are rising, both in children, adolescents and adults. Related to the impulse control phenotype, both preclinical and clinical studies have demonstrated lower γ-amino butyric acid (GABA) levels in prefrontal brain regions in ADHD. Whereas stimulant treatment increases GABA levels, preclinical studies have suggested that stimulant treatment effects may be age-dependent.As the long-term consequences of stimulant use in ADHD children and adolescents have so far been poorly studied, we used magnetic resonance spectroscopy to assess GABA+ and glutamate + glutamine (Glx) levels in the medial prefrontal cortex (mPFC) of adult ADHD patients, both before and after an oral methylphenidate (MPH) challenge. Three groups were studied: 1) ADHD patients who were first treated with stimulants before 16 years of age, i.e. during periods of ongoing brain development (early-stimulant-treated, EST); 2) patients first treated with stimulants in adulthood (i.e. > 23 years) (late-stimulant-treated, LST), and 3) stimulant-treatment-naive (STN) ADHD patients.Reduced basal GABA+ levels were found in EST compared to LST patients (p = 0.04), while after an MPH challenge, only the EST patients showed significant increases in GABA+ (p = 0.01). For Glx, no differences were found at baseline, nor after an MPH challenge.First stimulant exposure at a young age is thus associated with lower baseline levels of GABA+ and increased responsivity in adulthood. This effect could not be found in patients that started treatment at an adult age. Hence, while adult stimulant treatment seems to exert no major effects on GABA+ levels in the mPFC, MPH may induce long-lasting alterations in the adult mPFC GABAergic system when treatment was started at a young age.

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“…In addition, the differential effect of AMPH over K + ‐induced dopamine release in different brain regions could be due to region‐specific effects of AMPH depending on other AMPH‐sensitive neurotransmitter systems. For instance, acute systemic administration of AMPH does not increase LS DA extracellular levels but readily increases NAcc DA extracellular levels of the same animals (Sotomayor‐Zarate et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…In this sense, our laboratory group showed that acute systemic administration of morphine increases DA extracellular levels in the rat LS (Sotomayor et al, ). However, we have shown that acute systemic amphetamine (AMPH) administration does not induce an increase in DA extracellular levels in the LS (Sotomayor‐Zarate et al, ). In addition, we reported that direct intra LS infusion of AMPH increases LS DA extracellular levels and that the lack of effect with systemic AMPH depends on the activation of LS GABA B receptors.…”

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confidence: 99%

Withdrawal from chronic amphetamine reduces dopamine transmission in the rat lateral septum

Renard

Sotomayor‐Zárate

Blanco

et al. 2014

Journal of Neuroscience Research

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The lateral septum (LS) is a brain nucleus implicated in the addictive process. This study investigated whether withdrawal from chronic amphetamine (AMPH) induces alterations in dopamine (DA) transmission within the LS. Male Sprague-Dawley rats were injected with AMPH (2.5 mg/kg i.p.) or saline during 14 days and thereafter subjected to 24 hr or 14 days of withdrawal. After these withdrawal periods, we measured DA extracellular levels by in vivo microdialysis, DA tissue levels, and tyrosine hydroxylase (TH) and vesicular monoamine transporter-2 (VMAT2) expression in the LS. Our results showed a significant decrease in K(+) -induced release of DA in the LS of AMPH-treated rats, 14 days after withdrawal compared with saline-treated rats. There were no significant differences in DA tissue content and TH expression. Interestingly, there was a decrease of LS VMAT2 expression in AMPH-treated rats, 14 days after withdrawal compared with saline-treated rats. This is the first neurochemical evidence showing that withdrawal from repeated AMPH administration decreases K(+) -induced DA release in the rat LS. Our results suggest that this decrease in DA releasability could be due to a decrease in DA vesicular uptake. The possibility that these neurochemical changes are associated with AMPH abstinence syndrome should be further explored.

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Activation of GABA‐B receptors induced by systemic amphetamine abolishes dopamine release in the rat lateral septum

Cited by 25 publications

References 41 publications

4‐Methylthioamphetamine Increases Dopamine in the Rat Striatum and has Rewarding Effects In Vivo

4‐Methylthioamphetamine Increases Dopamine in the Rat Striatum and has Rewarding Effects In Vivo

Age-dependent, lasting effects of methylphenidate on the GABAergic system of ADHD patients

Withdrawal from chronic amphetamine reduces dopamine transmission in the rat lateral septum

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