Widespread reduction of dopamine cell bodies and terminals in adult rats exposed to a low dose regimen of MDMA during adolescence

Cadoni, C; Pisanu, Augusta; Simola, Nicola; Frau, Lucia; Porceddu, Pier Francesca; Corongiu, Silvia; Dessi, Christian; Sil, Annesha; Plumitallo, Antonio; Wardas, Jadwiga; Chiara, G. Di

doi:10.1016/j.neuropharm.2017.06.008

Cited by 19 publications

(9 citation statements)

References 68 publications

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“…Moreover, comparable effects on GABA and dopamine signaling in the PFC have been reported following adolescent exposure to the dopamine transporter blockers cocaine (Cass et al, 2013) and GBR 12909 (Khan et al, 2017), the substituted amphetamine MDMA (3,4-methylendioxymethamphetamine; Cadoni et al, 2017) or the cannabinoid receptor agonist WIN 55,212-2 (Cass et al, 2014) In summary, the results of the current study and others (Laviola et al, 2001;McPherson and Lawrence, 2006;Labonte et al, 2012;Reynolds et al, 2015;Kang et al, 2016a;TendillaBeltrán et al, 2016) point to a key role for drug-induced changes in the structural and functional development of the mesocorticolimbic dopamine system in the neural and behavioral changes induced by adolescent AMPH exposure. One intriguing possibility, which awaits testing, is that the phasic dopamine changes caused by an injection of AMPH have the unique ability to reorganize the structural and functional connections between the ventral tegmental area and the PFC in adolescents compared to adults.…”

Section: Discussionmentioning

confidence: 75%

Effects of amphetamine exposure during adolescence on behavior and prelimbic cortex neuron activity in adulthood

Sherrill¹,

Gulley²

2018

Preprint

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Repeated exposure to psychostimulants during adolescence produces long-lasting changes in behavior that may be mediated by disrupted development of the mesocorticolimbic dopamine system. Here, we tested this hypothesis by assessing the effects of amphetamine (AMPH) and dopamine receptor-selective drugs on behavior and neuron activity in the prelimbic region of the medial prefrontal cortex (PFC). Adolescent male, Sprague-Dawley rats were given saline or 3 mg/kg AMPH between postnatal day (P) 27 and P45. In Experiment 1, locomotor behavior was assessed during adulthood following challenges with a dopamine D1 (SKF 82958) or D2 (quinpirole) receptor-selective agonist. In Experiment 2, pre-exposed rats were challenged during adulthood with AMPH and a D1 (SKF 83566) or D2 (eticlopride) receptor-selective antagonist. In Experiment 3, the activity of putative pyramidal cells in the prelimbic cortex was recorded as rats behaved in an open-field arena before and after challenge injections with AMPH and one of the antagonists. We found that compared to controls, adolescent pre-exposed rats were more sensitive to the stimulant effects of AMPH and the dopamine receptor agonists, as well as to the ability of the antagonists to reverse AMPH-induced stereotypy. Prelimbic neurons from AMPH pre-exposed rats were also more likely to respond to an AMPH challenge in adulthood, primarily by reducing their activity, and the antagonists reversed these effects. Our results suggest that exposure to AMPH during adolescence leads to enduring adaptations in the mesocorticolimbic dopamine system that likely mediate heightened response to the drug during adulthood.

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Section: Discussionmentioning

confidence: 75%

Effects of amphetamine exposure during adolescence on behavior and prelimbic cortex neuron activity in adulthood

Sherrill¹,

Gulley²

2018

Preprint

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“…However, we have shown previously that adolescent AMPH exposure impairs D 1 -mediated inhibition of pyramidal neurons in the PFC (Kang et al, 2016a) and leads to disinhibition in these cells following AMPH challenge in adulthood (Paul et al, 2016). Moreover, comparable effects on GABA and dopamine signaling in the PFC have been reported following adolescent exposure to the dopamine transporter blockers cocaine (Cass et al, 2013) and GBR 12909 (Khan et al, 2017), the substituted amphetamine MDMA (3,4-methylendioxymethamphetamine; Cadoni et al, 2017) or the cannabinoid receptor agonist WIN 55,212-2 (Cass et al, 2014)…”

Section: Discussionmentioning

confidence: 84%

Effects of amphetamine exposure during adolescence on behavior and prelimbic cortex neuron activity in adulthood

Sherrill

Gulley

2018

Brain Research

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Repeated exposure to psychostimulants during adolescence produces long-lasting changes in behavior that may be mediated by disrupted development of the mesocorticolimbic dopamine system. Here, we tested this hypothesis by assessing the effects of amphetamine (AMPH) and dopamine receptor-selective drugs on behavior and neuron activity in the prelimbic region of the medial prefrontal cortex (PFC). Adolescent male, Sprague-Dawley rats were given saline or 3 mg/kg AMPH between postnatal day (P) 27 and P45. In Experiment 1, locomotor behavior was assessed during adulthood following challenges with a dopamine D (SKF 82958) or D (quinpirole) receptor-selective agonist. In Experiment 2, pre-exposed rats were challenged during adulthood with AMPH and a D (SKF 83566) or D (eticlopride) receptor-selective antagonist. In Experiment 3, the activity of putative pyramidal cells in the prelimbic cortex was recorded as rats behaved in an open-field arena before and after challenge injections with AMPH and one of the antagonists. We found that compared to controls, adolescent pre-exposed rats were more sensitive to the stimulant effects of AMPH and the dopamine receptor agonists, as well as to the ability of the antagonists to reverse AMPH-induced stereotypy. Prelimbic neurons from AMPH pre-exposed rats were also more likely to respond to an AMPH challenge in adulthood, primarily by reducing their activity, and the antagonists reversed these effects. Our results suggest that exposure to AMPH during adolescence leads to enduring adaptations in the mesocorticolimbic dopamine system that likely mediate heightened response to the drug during adulthood.

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“…Neurotoxic effects of MDMA on dopamine neurons were also reported in rats exposed to MDMA at a low dose, evidenced by the widespread reduction of the number of the neurons upon MDMA exposure (Cadoni et al, 2017;Costa, Morelli & Simola, 2017). Breivik et al (2014) also reported that long-term exposure of MDMA affected the serotonergic and dopaminergic transport systems in the rat brain.…”

Section: Effects Of Mdma On Neuronal Damagementioning

confidence: 88%

“…The NMDA receptor, a type of ionotropic glutamate receptors, was reported to be also involved in the rewarding effects of MDMA (Garcia-Pardo, Escobar-Valero, Rodriguez-Arias, Minarro, & Aguilar, 2015). MDMA-treated rats also displayed a deficit in recognition memory in the novel recognition test, which was believed to occur due to the damage to dopamine neurons (Cadoni et al, 2017). Hence, the effects of MDMA on memory are seen through the alterations in dopaminergic as well as the disruption of NMDA receptors.…”

Section: Effects Of Mdma On Memory and Learningmentioning

confidence: 99%

MDMA and the Brain: A Short Review on the Role of Neurotransmitters in the Cause of Neurotoxicity

Mustafa

Bakar

Mohamad

et al. 2019

Basic Clin. Neurosci. J.

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N-Methyl-3, 4-methylenedioxyamphetamine (MDMA), or ecstasy is a recreational drug of abuse. It is a synthetic substance that affects the body's systems, which its mechanism of action and treatment should be more investigated. MDMA provides an immediate enjoyable feeling by stimulating the release of neurotransmitters, such as dopamine and serotonin in the brain. Unfortunately, abnormal regulation of the brain neurotransmitters, as well as the increased oxidative stress causes damage to the brain neurons after the MDMA exposure. Only a few studies have been done regarding its treatment. Thus, the treatment of MDMA complications should be further explored mainly by targeting its mechanism of action in the neurotransmitter systems. Hence, this study presents a short review regarding the recent findings on the role of neurotransmitters to cause MDMA neurotoxicity. The results will be useful for future research in elucidating the potential treatment based on the targeted mechanisms to treat the neurotoxic effects of MDMA.

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Widespread reduction of dopamine cell bodies and terminals in adult rats exposed to a low dose regimen of MDMA during adolescence

Cited by 19 publications

References 68 publications

Effects of amphetamine exposure during adolescence on behavior and prelimbic cortex neuron activity in adulthood

Effects of amphetamine exposure during adolescence on behavior and prelimbic cortex neuron activity in adulthood

Effects of amphetamine exposure during adolescence on behavior and prelimbic cortex neuron activity in adulthood

MDMA and the Brain: A Short Review on the Role of Neurotransmitters in the Cause of Neurotoxicity

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