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Comparison of (+)-methamphetamine, ±-methylenedioxymethamphetamine, (+)-amphetamine and ±-fenfluramine in rats on egocentric learning in the Cincinnati water maze.
Synapse. 2011 May; 65(5):368-78.S

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 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.

Authors+Show Affiliations

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.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

20730798

Citation

Vorhees, Charles V., et al. "Comparison of (+)-methamphetamine, ±-methylenedioxymethamphetamine, (+)-amphetamine and ±-fenfluramine in Rats On Egocentric Learning in the Cincinnati Water Maze." Synapse (New York, N.Y.), vol. 65, no. 5, 2011, pp. 368-78.
Vorhees CV, He E, Skelton MR, et al. Comparison of (+)-methamphetamine, ±-methylenedioxymethamphetamine, (+)-amphetamine and ±-fenfluramine in rats on egocentric learning in the Cincinnati water maze. Synapse. 2011;65(5):368-78.
Vorhees, C. V., He, E., Skelton, M. R., Graham, D. L., Schaefer, T. L., Grace, C. E., Braun, A. A., Amos-Kroohs, R., & Williams, M. T. (2011). Comparison of (+)-methamphetamine, ±-methylenedioxymethamphetamine, (+)-amphetamine and ±-fenfluramine in rats on egocentric learning in the Cincinnati water maze. Synapse (New York, N.Y.), 65(5), 368-78. https://doi.org/10.1002/syn.20854
Vorhees CV, et al. Comparison of (+)-methamphetamine, ±-methylenedioxymethamphetamine, (+)-amphetamine and ±-fenfluramine in Rats On Egocentric Learning in the Cincinnati Water Maze. Synapse. 2011;65(5):368-78. PubMed PMID: 20730798.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparison of (+)-methamphetamine, ±-methylenedioxymethamphetamine, (+)-amphetamine and ±-fenfluramine in rats on egocentric learning in the Cincinnati water maze. AU - Vorhees,Charles V, AU - He,Elizabeth, AU - Skelton,Matthew R, AU - Graham,Devon L, AU - Schaefer,Tori L, AU - Grace,Curtis E, AU - Braun,Amanda A, AU - Amos-Kroohs,Robyn, AU - Williams,Michael T, Y1 - 2010/10/08/ PY - 2009/12/31/received PY - 2010/07/09/accepted PY - 2010/8/24/entrez PY - 2010/8/24/pubmed PY - 2011/6/24/medline SP - 368 EP - 78 JF - Synapse (New York, N.Y.) JO - Synapse VL - 65 IS - 5 N2 - (+)-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. SN - 1098-2396 UR - https://www.unboundmedicine.com/medline/citation/20730798/Comparison_of__+__methamphetamine_±_methylenedioxymethamphetamine__+__amphetamine_and_±_fenfluramine_in_rats_on_egocentric_learning_in_the_Cincinnati_water_maze_ L2 - https://doi.org/10.1002/syn.20854 DB - PRIME DP - Unbound Medicine ER -