Early loss of dopaminergic terminals in striosomes after MDMA administration to mice

Abstract

The amphetamine analogue 3,4‐methylenedioxymethamphetamine (MDMA or “Ecstasy”) is a popular drug of abuse which causes different neurotoxic effects in the mouse compared with the rat. In mice, MDMA produces damage to striatal dopamine terminals, having little long‐term effects on serotonin (5‐HT) containing neurons. A relevant feature of the striatum is its striosome/matrix compartmental organization; defined by different connexions, and functions. In this study we examined the long‐term effect induced by MDMA on tyrosine hydroxylase (TH) and dopamine transporter (DAT) immunoreactivity in the striosomes and matrix compartments of mouse striatum. Mice given MDMA showed significant reductions in TH and DAT immunostaining in striatum compared with control animals. Interestingly, this effect was considerably more pronounced in striosomes than in the matrix. These data provide the first evidence that striosomes and matrix compartments of the mouse striatum have differential vulnerability to MDMA and that the long‐term neurotoxicity induced by MDMA in mice is primarily associated with a loss of striosomal dopamine fibres. Synapse 62:80–84, 2008. © 2007 Wiley‐Liss, Inc.

The intriguing effects of ecstasy (MDMA) on cognitive function in mice subjected to a minimal traumatic brain injury (mTBI)

“…MDMA in mice is predominately selective to dopamine release and dopamine transporter (DAT) inhibition, in the same time in rats, the major activity of MDMA is on the serotonergic system (Capela et al 2009;Capela et al 2007;Colado et al 2001;Colado et al 2004). Even though both neurotransmitters are related to learning and memory, impairments in spatial learning are more influenced by dopamine than serotonin (Granado et al 2008;Kern et al;Petrasek and Stuchlik 2009). Additionally, stimulation of dopamine receptors may play an important role in synaptic plasticity and memory storage of motor behaviors (Kleim et al 2003;Simola et al 2009).…”

Methamphetamine Causes Degeneration of Dopamine Cell Bodies and Terminals of the Nigrostriatal Pathway Evidenced by Silver Staining

“…Immunostaining was carried out on free-floating sections with standard avidin-biotin immunocytochemical protocols (Granado et al, 2008a;Ortiz et al, 2010). Endogenous peroxidase activity was removed by incubation in 3% H 2 O 2 for 10 min.…”

Repeated doses of methylone, a new drug of abuse, induce changes in serotonin and dopamine systems in the mouse

“…Some differences among neurotoxicity cathinone literature can be partially due to differences in the employed dosing-regimen and the time of sacrifice. However, due to the mechanism of action and structural similarity between methylone and MDMA, we used similar doses and time of sacrifice assessed in MDMA neurotoxicity studies (Chipana et al, 2006;Granado et al, 2008;Sánchez et al, 2003;Mueller et al, 2013).…”