PMID- 8764359
OWN - NLM
STAT- MEDLINE
DCOM- 19960923
LR  - 20131121
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 278
IP  - 1
DP  - 1996 Jul
TI  - Co-administration of MDMA with drugs that protect against MDMA neurotoxicity 
      produces different effects on body temperature in the rat.
PG  - 258-67
AB  - The substituted amphetamine 3,4-methylenedioxymethamphetamine (MDMA) has been 
      shown to be neurotoxic to serotonin (5HT) terminals in the rat, and rat body 
      temperature (TEMP) has been shown to affect this neurotoxicity. This study looked 
      at the effect on CORE TEMP of three drugs that protect against MDMA neurotoxicity 
      in the rat. Male Holtzmann rats were injected with a control saline (SAL) 
      injection or with ketanserin (KET; 6 mg/kg), alpha-methyl-p-tyrosine (AMPT; 75 
      mg/kg) or fluoxetine (FLUOX; 10 mg/kg) before a 40-mg/kg MDMA or SAL injection. 
      CORE TEMP was recorded throughout the study using a noninvasive peritoneally 
      implanted temperature probe. Rats pretreated with KET had no change in CORE TEMP 
      until MDMA was injected, at which time an immediate hypothermia was seen that 
      continued for 180 minutes, with a peak low of 34.7 degrees C. Rats treated with 
      AMPT had no change in CORE TEMP until the MDMA was injected, at which time an 
      immediate hypothermia was seen that continued for 240 min., with a peak low of 
      34.3 degrees C. Two weeks later, brain regions were analyzed for 5-HT and 
      5-hydroxindole acetic acid levels. MDMA produced significant (P < .05) decreases 
      in 5-HT and 5-hydroxindole acetic acid levels in the frontal cortex, 
      somatosensory cortex, striatum and hippocampus, and pretreatment with KET or AMPT 
      prevented these depletions. When rats were given the KET/MDMA or AMPT/MDMA drug 
      injections and warmed to prevent hypothermia, the protection against 
      neurotoxicity was removed, which indicated that the hypothermia mediated the 
      protective effects of KET and AMPT. In comparison with the hypothermia seen with 
      AMPT or KET pretreatment, pretreatment with FLUOX had no effect on CORE TEMP. The 
      rats given the FLUOX/MDMA treatment did not have different CORE TEMPs than rats 
      given SAL/MDMA. The FLUOX pretreatment protected against MDMA-induced 5-HT and 
      5-hydroxindole acetic acid depletions in the frontal cortex, somatosensory 
      cortex, striatum and hippocampus. This study suggests that a decrease in CORE 
      TEMP may be a mechanism of protection against MDMA neurotoxicity by some drugs 
      but that there is also a mechanism of protection that is independent of a change 
      in body temperature.
FAU - Malberg, J E
AU  - Malberg JE
AD  - University of Chicago, Department of Pharmacological and Physiological Sciences, 
      Illinois, USA.
FAU - Sabol, K E
AU  - Sabol KE
FAU - Seiden, L S
AU  - Seiden LS
LA  - eng
GR  - DA-07255-01/DA/NIDA NIH HHS/United States
GR  - MA-00085/PHS HHS/United States
GR  - RSA-10562/RS/DRS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Drug Combinations)
RN  - 01K63SUP8D (Fluoxetine)
RN  - 42HK56048U (Tyrosine)
RN  - 97F9DE4CT4 (Ketanserin)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Body Temperature/*drug effects
MH  - Drug Combinations
MH  - Fluoxetine/pharmacology
MH  - Ketanserin/*pharmacology
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Rats
MH  - Tyrosine/pharmacology
EDAT- 1996/07/01 00:00
MHDA- 1996/07/01 00:01
CRDT- 1996/07/01 00:00
PHST- 1996/07/01 00:00 [pubmed]
PHST- 1996/07/01 00:01 [medline]
PHST- 1996/07/01 00:00 [entrez]
PST - ppublish
SO  - J Pharmacol Exp Ther. 1996 Jul;278(1):258-67.