PLoS Biology
July 9, 2015
Xavier Viñals, Estefanía Moreno, Laurence Lanfumey et al.
211 citations
Activation of cannabinoid CB1 receptors (CB1R) by delta9-tetrahydrocannabinol (THC) causes negative effects including memory deficits, limiting therapeutic use. Behavioral studies in mice lacking 5-HT2A receptors (5-HT2AR) showed a dissociation: THC's antinociceptive effects remained, but its amnesic, anxiolytic-like, and social interaction effects depended on 5-HT2AR, while hypolocomotor, hypothermic, anxiogenic, and antinociceptive effects did not. Biochemical studies revealed CB1R and 5-HT2AR form heteromers in brain regions involved in memory, altering cell signaling and G-protein coupling. Synthetic peptides disrupting heteromerization selectively prevented THC-induced memory impairments, identifying CB1R-5-HT2AR heteromers as targets to separate cognitive deficits from beneficial pain relief.
The International Journal of Neuropsychopharmacology
July 9, 2008
Thibault Renoir, Eleni Païzanis, Malika El Yacoubi et al.
58 citations
A single sentence summary is not possible because the abstract contains multiple distinct findings. Four weeks after administering MDMA to mice, the potency of a 5-HT1A receptor agonist to inhibit serotonin neuron firing in the dorsal raphe nucleus doubled, and the hypothermic response to 8-OH-DPAT increased, indicating supersensitivity of 5-HT1A autoreceptors. Brain serotonin levels decreased without changes in citalopram binding. MDMA treatment also reduced hippocampal cell proliferation by 30% and increased immobility in the forced swim test, suggesting depressive-like behavior. These effects were absent in mice lacking the serotonin transporter, indicating the transporter is required for these delayed, antidepressant-opposite effects that may contribute to MDMA-induced mood disorders.
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.