PLoS ONE
November 4, 2013
Alvaro Llorente‐berzal, Emma Puighermanal, Aurelijus Burokas et al.
43 citations
Adolescent rats given THC (the main psychoactive component of cannabis) and/or MDMA (ecstasy) showed lasting, sex-dependent changes in behavior and brain chemistry. MDMA reduced exploration and increased anxiety-like behavior shortly after treatment. Long-term, THC disrupted object recognition memory in females but not males. MDMA alone weakened prepulse inhibition (a measure of sensorimotor gating) at the loudest sound tested, while combining it with THC caused a similar deficit at a softer sound. In the brain, THC reduced Arc protein in the hippocampus of both sexes but in the frontal cortex only in females.
European Journal of Neuroscience
July 15, 2004
Patricia Robledo, Victoria Mendizábal, Jordi Ortuño et al.
40 citations
The rewarding effects of MDMA do not require µ-opioid receptors, unlike those of opioids, ethanol, nicotine, and THC. In mice lacking µ-opioid receptors, MDMA still produced a conditioned place preference and increased dopamine release in the nucleus accumbens, while decreasing dopamine metabolites DOPAC and HVA. Basal dopamine and metabolite levels were similar between knockout and wild-type mice. The findings indicate that MDMA's effects on dopamine neurons are independent of µ-opioid receptor activation.
The International Journal of Neuropsychopharmacology
October 14, 2010
María Juliana Orejarena, Laurence Lanfumey, Rafaël Maldonado et al.
38 citations
The serotonin 5-HT2A receptor plays a crucial role in the reinforcing and addictive properties of MDMA. In experiments with mice, those lacking the 5-HT2A receptor showed reduced self-administration of MDMA at both 0.125 and 0.25 mg/kg per infusion compared to normal mice. MDMA increased horizontal locomotion more in the knockout mice than in normal mice. Dopamine release in the nucleus accumbens was lower in knockout mice both at baseline and after MDMA challenge. Cue-induced reinstatement of MDMA-seeking behavior was blocked by a selective 5-HT2A receptor antagonist at 0.5 mg/kg. These findings suggest that 5-HT2A receptors are essential for MDMA's reinforcing effects and for relapse triggered by drug-associated cues, likely through modulation of dopamine activity in the brain's reward pathway.
Addiction Biology
January 19, 2012
Xavier Viñals, Rafaël Maldonado, Patricia Robledo
32 citations
Repeated high doses of MDMA (30 mg/kg) given to mice impaired working memory and cognitive flexibility, with deficits in recalling learned alternation behavior persisting five days after the last dose. The high dose also increased perseveration errors in an attentional set-shifting task, indicating reduced cognitive flexibility. These behavioral effects were not due to anhedonia, as saccharin preference remained unchanged. Although baseline dopamine levels in the striatum were unaffected, an acute MDMA challenge failed to increase dopamine outflow in mice that had received the high dose, suggesting reduced dopamine transporter function. Dopamine outflow recovered seven days later. The findings suggest that neurotoxic MDMA doses cause lasting impairments in recall and cognitive flexibility in mice.
Synapse
December 22, 2009
Ainhoa Plaza‐zabala, Fernando Berrendero, Juan Suárez et al.
3 citations
Repeated high doses of MDMA impaired mice's ability to learn and recall an active avoidance task. Pretreatment with a low dose (5 mg/kg) of the endogenous PPAR-α agonist oleoylethanolamide (OEA) partially protected against these deficits, while a higher dose (25 mg/kg) worsened them. MDMA also reduced dopamine transporter (DAT)-binding sites in the brain four days after the last dose, an effect prevented by both OEA doses. Coexpression of tyrosine-hydroxylase and PPAR-α receptors was observed in the striatum and substantia nigra pars compacta, suggesting OEA modulates MDMA-induced cognitive deficits through a DAT-independent mechanism.