PMID- 16362399
OWN - NLM
STAT- MEDLINE
DCOM- 20060614
LR  - 20221207
IS  - 0033-3158 (Print)
IS  - 0033-3158 (Linking)
VI  - 184
IP  - 2
DP  - 2006 Jan
TI  - Initial deficit and recovery of function after MDMA preexposure in rats.
PG  - 239-46
AB  - RATIONALE: 3,4-methylenedioxymethamphetamine (MDMA) exposure was reported to 
      result in deficits in serotonergic neurotransmission with concomitant behavioral 
      suppression and tolerance to MDMA. Some data have also suggested that the 
      neurochemical deficits recover over time, raising the question as to whether 
      behavioral suppression would show a similar recovery. OBJECTIVES: The possibility 
      of recovery of behavioral deficits was examined in the present study. Rats were 
      administered an MDMA pretreatment regimen that was shown to produce numerous 
      serotonergic deficits and behavioral suppression 2 weeks thereafter. The full 
      expression of MDMA-produced hyperactivity was dependent upon serotonergic 
      integrity, therefore, the present study aimed to determine whether MDMA 
      pretreated rats were tolerant to MDMA 2 weeks after exposure. Further, because 
      serotonergic deficits have shown recovery over time, similar behavioral tests 
      were conducted at a later time point to determine whether functional recovery was 
      evident. METHODS: MDMA-produced hyperactivity was measured at different 
      withdrawal periods (2 and 12 weeks) to determine initial effects and the 
      possibility of recovery of function. RESULTS: In saline-pretreated control rats, 
      +/-MDMA (0.0-10.0 mg/kg) produced a dose-dependent increase in locomotor 
      activity. Rats that had received prior exposure to MDMA (4 x 10 mg/kg MDMA 
      injections administered at 2 h intervals) demonstrated tolerance when the 
      activity was measured 2 weeks after pretreatment. For these rats, there was a 
      downward shift in the dose-effect curve for MDMA-produced hyperactivity. 
      MDMA-produced hyperactivity in rats that were tested 12 weeks after pretreatment 
      was, however, comparable to controls, suggesting recovery of function. 
      CONCLUSION: These data are consistent with the idea that high dose MDMA exposure 
      produces neuroadaptations that exhibit recovery with extended abstinence from the 
      drug.
FAU - Brennan, K A
AU  - Brennan KA
AD  - Victoria University of Wellington, School of Psychology, P.O. Box 600, 
      Wellington, New Zealand.
FAU - Schenk, S
AU  - Schenk S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20051216
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (Hallucinogens)
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - 333DO1RDJY (Serotonin)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - QUC7NX6WMB (Sertraline)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/*drug effects
MH  - Brain Chemistry/*drug effects
MH  - Dose-Response Relationship, Drug
MH  - Hallucinogens/*pharmacology
MH  - Male
MH  - Motor Activity/drug effects
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Serotonin/*physiology
MH  - Selective Serotonin Reuptake Inhibitors/pharmacokinetics
MH  - Sertraline/pharmacokinetics
MH  - Synaptic Transmission/drug effects
EDAT- 2005/12/20 09:00
MHDA- 2006/06/15 09:00
CRDT- 2005/12/20 09:00
PHST- 2005/09/07 00:00 [received]
PHST- 2005/11/16 00:00 [accepted]
PHST- 2005/12/20 09:00 [pubmed]
PHST- 2006/06/15 09:00 [medline]
PHST- 2005/12/20 09:00 [entrez]
AID - 10.1007/s00213-005-0278-y [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2006 Jan;184(2):239-46. doi: 
      10.1007/s00213-005-0278-y. Epub 2005 Dec 16.