Comparison of (+)-methamphetamine, ±-methylenedioxymethamphetamine, (+)-amphetamine and ±-fenfluramine in rats on egocentric learning in the Cincinnati water maze.
(+)-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 x 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.
Vorhees
Charles V
CV
Division of Neurology, Department of Pediatrics, Cincinnati Children's Research Foundation and University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA. charles.vorhees@cchmc.org
He
Elizabeth
E
Skelton
Matthew R
MR
Graham
Devon L
DL
Schaefer
Tori L
TL
Grace
Curtis E
CE
Braun
Amanda A
AA
Amos-Kroohs
Robyn
R
Williams
Michael T
MT
D000661:Amphetamine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003080:Cold Temperature; D005277:Fenfluramine / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008694:Methamphetamine / Q000494:pharmacology; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018490:Serotonin Agents / Q000494:pharmacology*; D013037:Spatial Behavior / Q000187:drug effects*; D013550:Swimming; D013997:Time Factors
D000697:Central Nervous System Stimulants; D018490:Serotonin Agents; D005277:Fenfluramine; D008694:Methamphetamine; D000661:Amphetamine; D018817:N-Methyl-3,4-methylenedioxyamphetamine