PMID- 18241937
OWN - NLM
STAT- MEDLINE
DCOM- 20080701
LR  - 20131121
IS  - 0166-4328 (Print)
IS  - 0166-4328 (Linking)
VI  - 189
IP  - 1
DP  - 2008 May 16
TI  - Behavioral and neurochemical consequences of multiple MDMA administrations in the 
      rat: role of individual differences in anxiety-related behavior.
PG  - 52-64
LID - 10.1016/j.bbr.2007.12.008 [doi]
AB  - Using the elevated plus-maze (EPM), Wistar rats can be distinguished into high 
      (HA) or low anxiety (LA) subjects. These differences seem to reflect traits, 
      since HA and LA rats vary also in other anxiety-dependent tasks, neurochemical 
      mechanisms, and psychopharmacological reactivity, including lasting consequences 
      after single treatment with 3,4-methylenedioxymethamphetamine (MDMA). Here, we 
      tested whether multiple MDMA treatments also have subject-dependent effects. 
      Based on routine EPM screening, male Wistar rats were divided into HA and LA 
      sub-groups, which received five (i.e. multiple) daily injections of MDMA (5 
      mg/kg) or saline, followed by a test battery, including a challenge test with 
      MDMA, a retest in the EPM, a novel-object test, and a final neurochemical 
      analysis. Acutely, MDMA led to comparable hyperactivity in HA and LA rats. After 
      multiple MDMA, behavioral sensitization was observed, especially in LA rats. Open 
      arm time during the EPM retest (min 0-5) correlated with that of the initial one 
      only in those rats, which had received a single injection of MDMA. Rats with 
      multiple MDMA, especially LA-rats, showed more open-arm time and locomotion 
      during the subsequent 5-10 min of the retest. In a novel-object test, rats with 
      multiple MDMA, again especially LA subjects, showed more exploratory bouts 
      towards the novel object. Neurochemically, multiple MDMA led to moderately lower 
      serotonin in the ventral striatum, and higher dopamine levels in the frontal 
      cortex as compared to single MDMA; these effects were also moderated by 
      subject-dependent factors. Our data show that low-dosed multiple MDMA can lead to 
      behavioral sensitization and outlasting consequences, which affect behavior in 
      the EPM and a novel object task. Detecting such sequels partly requires 
      consideration of individual differences.
FAU - Ludwig, V
AU  - Ludwig V
AD  - Experimental and Physiological Psychology, Philipps-University of Marburg, 
      Gutenbergstr. 18, 35037 Marburg, Germany.
FAU - Mihov, Y
AU  - Mihov Y
FAU - Schwarting, R K W
AU  - Schwarting RK
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071223
PL  - Netherlands
TA  - Behav Brain Res
JT  - Behavioural brain research
JID - 8004872
RN  - 0 (Hallucinogens)
RN  - 0 (Neurotransmitter Uptake Inhibitors)
RN  - 333DO1RDJY (Serotonin)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Anxiety/*metabolism
MH  - Behavior, Animal/*drug effects
MH  - Dopamine/metabolism
MH  - Drug Administration Schedule
MH  - Exploratory Behavior/drug effects
MH  - Hallucinogens/*administration & dosage
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*administration & dosage/pharmacology
MH  - Neostriatum/*drug effects/metabolism
MH  - Neurotransmitter Uptake Inhibitors/administration & dosage/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Serotonin/metabolism
MH  - Statistics, Nonparametric
EDAT- 2008/02/05 09:00
MHDA- 2008/07/02 09:00
CRDT- 2008/02/05 09:00
PHST- 2007/12/05 00:00 [received]
PHST- 2007/12/10 00:00 [accepted]
PHST- 2008/02/05 09:00 [pubmed]
PHST- 2008/07/02 09:00 [medline]
PHST- 2008/02/05 09:00 [entrez]
AID - S0166-4328(07)00659-6 [pii]
AID - 10.1016/j.bbr.2007.12.008 [doi]
PST - ppublish
SO  - Behav Brain Res. 2008 May 16;189(1):52-64. doi: 10.1016/j.bbr.2007.12.008. Epub 
      2007 Dec 23.