PMID- 2573905
OWN - NLM
STAT- MEDLINE
DCOM- 19891229
LR  - 20191210
IS  - 0091-3057 (Print)
IS  - 0091-3057 (Linking)
VI  - 33
IP  - 3
DP  - 1989 Jul
TI  - Long-term central 5-HT depletions resulting from repeated administration of MDMA 
      enhances the effects of single administration of MDMA on schedule-controlled 
      behavior of rats.
PG  - 641-8
AB  - The behavioral effect of single administration of +/- 
      3,4-methylene-dioxymethamphetamine (MDMA) on rats performing on the 
      differential-reinforcement-of-low-rate 72-second schedule (DRL 72-sec) was 
      compared before and after a period of repeated administration of MDMA known to 
      deplete 5-hydroxytryptamine (5-HT) levels in the brain. Single administration of 
      MDMA decreased reinforcement rate (1, 2, 4, 6 mg/kg) and increased response rate 
      (4,6 mg/kg) of rats performing on the DRL 72-sec schedule. This effect is typical 
      of amphetamines and other psychomotor stimulants. Four weeks after repeated 
      administration of MDMA (6 mg/kg twice daily for 4 days) there was an increase in 
      sensitivity to the effect of single administration of MDMA. Doses of 2, 4 and 6 
      mg/kg of MDMA resulted in increases in response rate that were significantly 
      greater after repeated MDMA administration than before. Doses of 0.5, 2, and 6 
      mg/kg of MDMA resulted in decreases of reinforcement rate that were significantly 
      greater after repeated MDMA administration than before. Repeated administration 
      of MDMA resulted in long-term depletion of serotonin levels by 30-50% in the 
      amygdala, neostriatum, hippocampus and the frontal cortex. Norepinephrine and 
      dopamine (DA) levels were not significantly different from control in any of the 
      brain regions analyzed. The behavioral and neurochemical results suggest that 
      serotonergic neurons normally exert an inhibitory action upon the psychomotor 
      stimulant effects of MDMA. Since the psychomotor stimulant effects of 
      amphetamines appear to be mediated primarily by the dopamine system, these 
      results provide evidence that 5-HT and DA may represent opposing systems in the 
      DRL schedule-controlled behavior.
FAU - Li, A A
AU  - Li AA
AD  - University of Chicago, Department of Pharmacological and Physiological Sciences, 
      IL 60637.
FAU - Marek, G J
AU  - Marek GJ
FAU - Vosmer, G
AU  - Vosmer G
FAU - Seiden, L S
AU  - Seiden LS
LA  - eng
GR  - 5 T32 GM07281/GM/NIGMS NIH HHS/United States
GR  - MH 11191/MH/NIMH NIH HHS/United States
GR  - MH-10562/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Pharmacol Biochem Behav
JT  - Pharmacology, biochemistry, and behavior
JID - 0367050
RN  - 0 (Amphetamines)
RN  - 0 (Biogenic Monoamines)
RN  - 333DO1RDJY (Serotonin)
RN  - 4764-17-4 (3,4-Methylenedioxyamphetamine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - 3,4-Methylenedioxyamphetamine/administration & dosage/analogs & 
      derivatives/*pharmacology
MH  - Amphetamines/*pharmacology
MH  - Animals
MH  - Behavior, Animal/*drug effects
MH  - Biogenic Monoamines/metabolism
MH  - Brain Chemistry/*drug effects
MH  - Conditioning, Psychological/drug effects
MH  - Dopamine/analysis/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine
MH  - Rats
MH  - Rats, Inbred Strains
MH  - *Reinforcement Schedule
MH  - Serotonin/analysis/*deficiency/metabolism
MH  - Time Factors
EDAT- 1989/07/01 00:00
MHDA- 1989/07/01 00:01
CRDT- 1989/07/01 00:00
PHST- 1989/07/01 00:00 [pubmed]
PHST- 1989/07/01 00:01 [medline]
PHST- 1989/07/01 00:00 [entrez]
AID - 0091-3057(89)90402-4 [pii]
AID - 10.1016/0091-3057(89)90402-4 [doi]
PST - ppublish
SO  - Pharmacol Biochem Behav. 1989 Jul;33(3):641-8. doi: 10.1016/0091-3057(89)90402-4.