PMID- 17415794 OWN - NLM STAT- MEDLINE DCOM- 20070710 LR - 20181113 IS - 0887-4476 (Print) IS - 1098-2396 (Electronic) IS - 0887-4476 (Linking) VI - 61 IP - 7 DP - 2007 Jul TI - Developmental effects of +/-3,4-methylenedioxymethamphetamine on spatial versus path integration learning: effects of dose distribution. PG - 488-99 AB - We previously demonstrated that postnatal day 11-20 +/-3,4-methylenedioxymethamphetamine (MDMA) exposure reduces locomotor activity and impairs path integration and spatial learning independent of the effects on activity. The effects were seen when the drug was administered twice per day, but the optimal dosing regimen is unknown. We tested whether the same total daily dose of MDMA administered in different patterns would equally affect later behavior. A split-litter design (15 litters) was used with one male/female pair per litter receiving one of four treatment regimens. All offspring received four injections per day on P11-20 as follows: 40 x 1 (40 mg/kg MDMA x 1 + saline x 3), 20 x 2 (20 mg/kg MDMA x 2 + saline x 2), 10 x 4 (10 mg/kg MDMA x 4), or Saline (saline x 4). Doses were spaced 2 h apart. Group 40 x 1 received MDMA as the first daily dose followed by three saline doses; group 20 x 2 received MDMA as the first and last dose and saline for the middle two doses; group 10 x 4 received MDMA for all four doses; and the saline group received saline for all four doses. Regardless of dose schedule, all groups treated with MDMA exhibited reduced locomotor activity. No MDMA effects were found on swimming ability in a straight channel. Modest MDMA effects were found on Barnes maze performance. The major findings were that the 40 x 1 and 20 x 2 MDMA groups showed impaired Cincinnati multiple T-water-maze learning and the 10 x 4 and 20 x 2 MDMA groups showed impaired Morris water maze learning. The results suggest that MDMA dose distribution has a long-term differential effect on different types of learning. Dose distribution warrants greater attention in the design of developmental drug studies along with the standard considerations of dose and age. FAU - Vorhees, Charles V AU - Vorhees CV AD - Division of Neurology, Cincinnati Children's Research Foundation and University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA. charles.vorhees@cchmc.org FAU - Schaefer, Tori L AU - Schaefer TL FAU - Williams, Michael T AU - Williams MT LA - eng GR - K01 DA014269-05/DA/NIDA NIH HHS/United States GR - R01 DA021394-03/DA/NIDA NIH HHS/United States GR - DA006733/DA/NIDA NIH HHS/United States GR - K01 DA014269/DA/NIDA NIH HHS/United States GR - R01 DA021394/DA/NIDA NIH HHS/United States GR - DA021394/DA/NIDA NIH HHS/United States GR - T32 ES007051/ES/NIEHS NIH HHS/United States GR - R01 DA006733/DA/NIDA NIH HHS/United States GR - DA014269/DA/NIDA NIH HHS/United States GR - R01 DA006733-17/DA/NIDA NIH HHS/United States GR - T32 ES007051-34/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Synapse JT - Synapse (New York, N.Y.) JID - 8806914 RN - 0 (Serotonin Agents) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) SB - IM MH - Age Factors MH - Analysis of Variance MH - Animals MH - Animals, Newborn MH - Behavior, Animal/drug effects MH - Body Weight/drug effects MH - Dose-Response Relationship, Drug MH - Drug Administration Schedule MH - Exploratory Behavior/drug effects MH - Female MH - Learning/*drug effects MH - Maze Learning/drug effects MH - Motor Activity/*drug effects MH - N-Methyl-3,4-methylenedioxyamphetamine/*administration & dosage MH - Pregnancy MH - Rats MH - Reaction Time/drug effects MH - Serotonin Agents/*administration & dosage MH - Spatial Behavior/*drug effects PMC - PMC2888320 MID - NIHMS207860 EDAT- 2007/04/07 09:00 MHDA- 2007/07/11 09:00 PMCR- 2010/06/21 CRDT- 2007/04/07 09:00 PHST- 2007/04/07 09:00 [pubmed] PHST- 2007/07/11 09:00 [medline] PHST- 2007/04/07 09:00 [entrez] PHST- 2010/06/21 00:00 [pmc-release] AID - 10.1002/syn.20379 [doi] PST - ppublish SO - Synapse. 2007 Jul;61(7):488-99. doi: 10.1002/syn.20379.