Comparison of (+)-methamphetamine, ±}-methylenedioxymethamphetamine (MDMA), (+)-amphetamine and ±}-fenfluramine in rats on egocentric learning in the Cincinnati water maze
Charles V. Vorhees, Elizabeth He, Matthew R. Skelton, Devon L Graham, Tori L. Schaefer, Curtis E. Grace, Amanda A. Braun, Robyn M. Amos‐kroohs, Michael T. Williams
Synapse October 8, 2010 DOI: 10.1002/syn.20854 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | Methamphetamine Amphetamine MDMA Fenfluramine |
| Dose | MA 10 or 12.5 mg/kg/dose, AMPH 25 mg/kg/dose, MDMA 15 mg/kg/dose, FEN 16.5 mg/kg/dose, each given four times at 2-hour intervals |
| Duration | Single-day dosing, testing began two weeks later and lasted 21 days |
| Measures | Cincinnati water maze (CWM) errors and latency, swim speed |
| Topics | MDMA |
| Key findings | Amphetamine and methamphetamine (both doses) increased errors and latency in the Cincinnati water maze, while MDMA and fenfluramine had no significant effect, suggesting egocentric learning may be dopaminergically mediated. |
Abstract
(+)‐Methamphetamine (MA), (±)‐3,4‐methylenedioxymethamphetamine (MDMA), (+)‐amphetamine (AMPH), and (±)‐fenfluramine (FEN) are phenylethylamines with CNS effects. At higher doses, each induces protracted reductions in brain dopamine (DA) and/or serotonin. Chronic MA and MDMA users show persistent monoamine reductions and cognitive impairments. In rats, similar neurochemical effects can be induced, yet cognitive impairments have been difficult to demonstrate. We recently showed that rats treated on a single day with MA (10 mg/kg × 4 at 2 h intervals) exhibit impaired egocentric learning (Cincinnati water maze [CWM]) without affecting spatial learning (Morris water maze [MWM]) (Herring et al., [ 2008 ] Psychopharmacology (Berl) 199:637–650). Whether this effect is unique to MA or is a general characteristic of these drugs is unknown. Accordingly, this experiment compared these drugs on CWM performance. Drugs were given s.c. in four doses at 2 h intervals. MA doses were 10 or 12.5 mg/kg/dose, AMPH 25 mg/kg/dose (to match MA12.5‐induced hyperthermia), MDMA 15 mg/kg/dose (previously established hyperthermia‐inducing dose), and FEN 16.5 mg/kg/dose (equimolar to MA12.5). Two weeks later, rats were tested in the CWM (2 trials/day, 21 days). AMPH and MA (both doses) induced significant increases in CWM errors and latency to reach the goal with no differences in swim speed. MDMA and FEN did not significantly alter learning. Given that FEN selectively and MDMA preferentially affect serotonin whereas AMPH selectively and MA preferentially affect DA, the data suggest that egocentric learning may be predominantly dopaminergically mediated. Synapse, 2010. © 2010 Wiley‐Liss, Inc.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 5
- Cognitive impairments from developmental exposure to serotonergic drugs: citalopram and MDMA The International Journal of Neuropsychopharmacology January 11, 2013
- Electroencephalographic and convulsive effects of binge doses of (+)-methamphetamine, 5-methoxydiisopropyltryptamine, and (±)-3,4-methylenedioxymethamphetamine in rats. The open neuropsychopharmacology journal 2012
- Neuronal reorganization in adult rats neonatally exposed to (±)-3,4-methylenedioxymethamphetamine Toxicology Reports October 11, 2016
- Cognitive Effects of MDMA in Laboratory Animals: A Systematic Review Focusing on Dose. Pharmacological Reviews July 1, 2019
- Comparative effects of amphetamine-like psychostimulants on rat hippocampal cell genesis at different developmental ages. Neurotoxicology September 2016
Cites 9
- Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs BMC Pharmacology March 3, 2006
- Memory impairment in abstinent MDMA ("Ecstasy") users Neurology December 1, 1998
- Impaired cognitive performance in drug free users of recreational ecstasy (MDMA) Journal of Neurology, Neurosurgery, and Psychiatry June 1, 2000
- 5‐HT loss in rat brain following 3, 4‐methylenedioxymethamphetamine (MDMA), p‐chloroamphetamine and fenfluramine administration and effects of chlormethiazole and dizocilpine British Journal of Pharmacology March 1, 1993
- (+/-)-3,4-Methylenedioxymethamphetamine treatment in adult rats impairs path integration learning: a comparison of single vs once per week treatment for 5 weeks. Neuropharmacology December 2008
and 4 more in the library