methylone and Memory-Disorders

Methylone is a cathinone derivative that has recently emerged as a designer drug of abuse in Europe and the USA. Studies on the acute and long-term neurotoxicity of cathinones are starting to be conducted. We investigated the neurochemical/enzymatic changes indicative of neurotoxicity after methylone administration (4 × 20 mg/kg, subcutaneously, per day with 3 h intervals) to adolescent rats, to model human recreational use. In addition, we studied the effect of methylone on spatial learning ad memory using the Morris water maze paradigm. Our experiments were carried out at a high ambient temperature to simulate the hot conditions found in dance clubs where the drug is consumed. We observed a hyperthermic response to methylone that reached a peak 30 min after each dose. We determined a serotonergic impairment in methylone-treated rats, especially in the frontal cortex, where it was accompanied by astrogliosis. Some serotonergic alterations were also present in the hippocampus and striatum. No significant neurotoxic effect on the dopaminergic system was identified. Methylone-treated animals only displayed impairments in the probe trial of the Morris water maze, which concerns reference memory, while the spatial learning process seemed to be preserved.

Topics: Animals; Corpus Striatum; Designer Drugs; Dopamine Plasma Membrane Transport Proteins; Frontal Lobe; Gliosis; Hippocampus; Male; Maze Learning; Memory Disorders; Methamphetamine; Neurotoxicity Syndromes; Radioligand Assay; Rats; Receptor, Serotonin, 5-HT2A; Serotonergic Neurons; Serotonin Plasma Membrane Transport Proteins; Tryptophan Hydroxylase; Tyrosine 3-Monooxygenase

The use of cathinone-derivative designer drugs methylone and mephedrone has increased rapidly in recent years. Our aim was to investigate the possible long-term effects of these drugs on a range of behavioral tests in mice. Further, we investigated the long-term effects of these drugs on brain neurochemistry in both rats and mice.. We treated animals with a binge-like regimen of methylone or mephedrone (30 mg/kg, twice daily for 4 days) and, starting 2 weeks later, we performed behavioral tests of memory, anxiety and depression and measured brain levels of dopamine (DA), serotonin (5-HT), their metabolites and norepinephrine (NE). 5-HT and DA transporter (5-HTT and DAT) levels were also measured in rats by [(3)H]paroxetine and [(3)H]mazindol binding.. Mephedrone reduced working memory performance in the T-maze spontaneous alternation task but did not affect neurotransmitter levels aside from a 22% decrease in striatal homovanillic acid (HVA) levels in mice. Methylone had little effect on behavior or neurotransmitter levels in mice but produced a widespread depletion of 5-HT and 5-HTT levels in rats.. Both methylone and mephedrone appeared to have a long-term effect on either behavioral or biochemical gauges of neurotoxicity in rodents.

Topics: Animals; Anxiety; Brain; Depression; Designer Drugs; Disease Models, Animal; Dopamine; Dopamine Plasma Membrane Transport Proteins; Hindlimb Suspension; Male; Maze Learning; Memory Disorders; Methamphetamine; Mice; Mice, Inbred C57BL; Norepinephrine; Radioligand Assay; Rats; Rats, Wistar; Serotonin; Serotonin Plasma Membrane Transport Proteins