RATIONALE: 3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is a widely used recreational drug known to cause selective long-term serotonergic damage. OBJECTIVES: The aim of this study was to characterize the ultrastructure of serotonergic pericarya and proximal neurites in the dorsal raphe nucleus as well as the ultrastructure of serotonergic axons in the frontal cortex of adolescent Dark Agouti rats 3 days after treatment with 15 mg/kg i.p. MDMA. METHODS: Light microscopic immunohistochemistry and pre-embedding immunoelectron microscopy with a novel tryptophan hydroxylase-2 (Tph2) specific antibody, as a marker of serotonergic structures. RESULTS: Light microscopic analysis showed reduced serotonergic axon density and aberrant swollen varicosities in the frontal cortex of MDMA-treated animals. According to the electron microscopic analysis, Tph2 exhibited diffuse cytoplasmic immunolocalization in dorsal raphe neuronal cell bodies. The ultrastructural-morphometric analysis of these cell bodies did not indicate pathological changes or significant alteration in the cross-sectional areal density of any examined organelles. Proximal serotonergic neurites in the dorsal raphe exhibited no ultrastructural alteration. However, in the frontal cortex among intact fibers, numerous serotonergic axons with destructed microtubules were found. Most of their mitochondria were intact, albeit some injured axons also contained degenerating mitochondria; moreover, a few of them comprised confluent membrane whorls only. CONCLUSIONS: Our treatment protocol does not lead to ultrastructural alteration in the serotonergic dorsal raphe cell bodies and in their proximal neurites but causes impairment in cortical serotonergic axons. In these, the main ultrastructural alteration is the destruction of microtubules although a smaller portion of these axons probably undergo an irreversible damage.
RATIONALE: 3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is a widely used recreational drug known to cause selective long-term serotonergic damage. OBJECTIVES: The aim of this study was to characterize the ultrastructure of serotonergic pericarya and proximal neurites in the dorsal raphe nucleus as well as the ultrastructure of serotonergic axons in the frontal cortex of adolescent Dark Agouti rats 3 days after treatment with 15 mg/kg i.p. MDMA. METHODS: Light microscopic immunohistochemistry and pre-embedding immunoelectron microscopy with a novel tryptophan hydroxylase-2 (Tph2) specific antibody, as a marker of serotonergic structures. RESULTS: Light microscopic analysis showed reduced serotonergic axon density and aberrant swollen varicosities in the frontal cortex of MDMA-treated animals. According to the electron microscopic analysis, Tph2 exhibited diffuse cytoplasmic immunolocalization in dorsal raphe neuronal cell bodies. The ultrastructural-morphometric analysis of these cell bodies did not indicate pathological changes or significant alteration in the cross-sectional areal density of any examined organelles. Proximal serotonergic neurites in the dorsal raphe exhibited no ultrastructural alteration. However, in the frontal cortex among intact fibers, numerous serotonergic axons with destructed microtubules were found. Most of their mitochondria were intact, albeit some injured axons also contained degenerating mitochondria; moreover, a few of them comprised confluent membrane whorls only. CONCLUSIONS: Our treatment protocol does not lead to ultrastructural alteration in the serotonergic dorsal raphe cell bodies and in their proximal neurites but causes impairment in cortical serotonergic axons. In these, the main ultrastructural alteration is the destruction of microtubules although a smaller portion of these axons probably undergo an irreversible damage.
Authors: D Weissmann; M F Belin; M Aguera; C Meunier; M Maitre; C D Cash; M Ehret; P Mandel; J F Pujol Journal: Neuroscience Date: 1987-10 Impact factor: 3.590
Authors: Thomas J R Beveridge; Annis O Mechan; Marie Sprakes; Qi Pei; Tyra S C Zetterstrom; A Richard Green; J Martin Elliott Journal: Psychopharmacology (Berl) Date: 2004-01-20 Impact factor: 4.530
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Authors: Yunju Jin; Sarah E Dougherty; Kevin Wood; Landy Sun; Robert H Cudmore; Aya Abdalla; Geetha Kannan; Mikhail Pletnikov; Parastoo Hashemi; David J Linden Journal: Neuron Date: 2016-08-04 Impact factor: 17.173
Authors: Csaba Adori; Teresa Daraio; Raoul Kuiper; Swapnali Barde; Lubica Horvathova; Takashi Yoshitake; Robert Ihnatko; Ismael Valladolid-Acebes; Pauline Vercruysse; Ashley M Wellendorf; Roberto Gramignoli; Bela Bozoky; Jan Kehr; Elvar Theodorsson; Jose A Cancelas; Boris Mravec; Carl Jorns; Ewa Ellis; Jan Mulder; Mathias Uhlén; Christina Bark; Tomas Hökfelt Journal: Sci Adv Date: 2021-07-21 Impact factor: 14.136