Widespread reduction of dopamine cell bodies and terminals in adult rats exposed to a low dose regimen of MDMA during adolescence. (1st September 2017)

• Record Type: Journal Article
• Authors: Cadoni, Cristina; Pisanu, Augusta; Simola, Nicola; Frau, Lucia; Porceddu, Pier Francesca; Corongiu, Silvia; Dessì, Christian; Sil, Annesha; Plumitallo, Antonio; Wardas, Jadwiga; Di Chiara, Gaetano
• Is Part Of: Neuropharmacology. Volume 123(2017)
• Page Start: 385
• Page End: 394
• Publication Date: 2017-09-01
• Subjects: MDMA -- Caffeine -- Sensitization -- tyrosine hydroxylase -- Nucleus accumbens -- Neurotoxicity -- Recognition memory; NAc nucleus accumbens -- CPu caudate-putamen -- VTA ventral tegmental area -- SNc substantia nigra pars compacta -- TH tyrosine hydroxylase -- DAT dopamine transporter -- NORT novel object recognition test; Caffeine (PubChem CID: 2519) -- 3, 4-methylendioxymethamphetamine (PubChem CID: 1615); Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2017.06.008
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Although MDMA (3, 4-methylendioxymethamphetamine, ecstasy) neurotoxicity in serotonin neurons is largely recognized in a wide variety of species including man, neurotoxicity in dopamine (DA) neurons is thought to be species-specific. MDMA is mainly consumed by adolescents, often in conjunction with caffeine ( Energy Drinks ) and this association has been reported to exacerbate MDMA toxic effects. In order to model these aspects of MDMA use, vis-à-vis their impact on DA neurons, we investigated the effects of adolescent exposure to low doses of MDMA (5 mg/kg for 10 days), alone or in combination with caffeine (10 mg/kg) on neuronal and functional DA indices and on recognition memory in adult rats. MDMA reduced density of tyrosine hydroxylase (TH) positive neurons in the ventral tegmental area and in the substantia nigra pars compacta, and immunoreactivity of TH and DA transporter in the nucleus accumbens (NAc) shell and core, and caudate-putamen. This same treatment caused a reduction of basal dialysate DA in the NAc core. MDMA-pretreated rats also showed behavioral sensitization to a MDMA challenge at adulthood and potentiation of MDMA-induced increase of dialysate DA in the NAc core, but not in the NAc shell. In addition, MDMA-treated rats displayed a deficit in recognition memory. Caffeine co-administration did not affect the above outcomes. Our results show that adolescent exposure of rats to low doses of MDMA induces long-lasting and widespread reduction of DA neurons indicative of a neurotoxic effect on DA neurons and suggestive of a degeneration of the same neurons. Highlights: Adolescent exposure to MDMA causes a loss of DA neurons in rat VTA and SNc. Adolescent MDMA exposure impairs recognition memory at adulthood. Impaired recognition memory appears to be associated with reduced DA levels in NAc core. MDMA sensitization is associated with an increase in DA response in the NAc core.