PMID- 8632359
OWN - NLM
STAT- MEDLINE
DCOM- 19960703
LR  - 20161123
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 276
IP  - 2
DP  - 1996 Feb
TI  - Methylenedioxymethamphetamine-induced serotonin deficits are followed by partial 
      recovery over a 52-week period. Part II: Radioligand binding and autoradiography 
      studies.
PG  - 855-65
AB  - In our study, age-matched Holtzman Sprague-Dawley rats (275-300 g) received 
      injections with either saline (0.9%) or 3,4-methylenedioxymethamphetamine (MDMA; 
      20 mg/kg free base, s.c) twice daily for 4 days and allowed to recover for 2, 8, 
      16, 32 and 52 wk after the final injection before death. Radioligand binding 
      studies with 125I-RTI-55 to dopamine uptake sites in striatal homogenates showed 
      no effect of MDMA on the density of dopamine uptake sites. In contrast, 
      saturation binding studies with 125I-RTI-55 to 5-HT uptake sites in hippocampal 
      and frontal-parietal homogenates showed a significant reduction in the number of 
      uptake sites at 2 wk after MDMA treatment (34 and 25%, respectively of controls). 
      By 16 wk, a partial recovery in the number of 5-HT uptake sites was observed in 
      both tissues; however, only a full recovery of serotonin uptake sites was 
      observed in hippocampus at the end of 52 wk. In more detailed studies using 
      autoradiography with 125I-RTI-55, recovery of serotonin uptake sites varied from 
      region to region. In particular, recovery of 5-HT uptake sites in cerebral cortex 
      was observed to follow a rostral-caudal gradient. In addition, recovery of 5-HT 
      uptake site in hippocampus also followed a rostral-caudal gradient. Different 
      rates of recovery of 5-HT uptake sites were also observed for cingulate cortex, 
      laterodorsal thalamus and ventromedial hypothalamus. No effect of MDMA was 
      observed over lateral hypothalamus, substantia nigra and ventral tegmental area, 
      or over serotonergic cell bodies such as dorsal raphe and median raphe. In 
      conclusion, our study is consistent with previous studies describing the 
      selective neurotoxicity of MDMA for serotonin neurons and presents evidence 
      showing the rate of recovery of 5-HT uptake sites varies according to region and 
      that recovery of 5-HT uptake sites in neocortex and hippocampus follows a 
      rostral-caudal gradient.
FAU - Lew, R
AU  - Lew R
AD  - University of Chicago, Department of Pharmacological and Physiological Sciences, 
      IL 60637, USA.
FAU - Sabol, K E
AU  - Sabol KE
FAU - Chou, C
AU  - Chou C
FAU - Vosmer, G L
AU  - Vosmer GL
FAU - Richards, J
AU  - Richards J
FAU - Seiden, L S
AU  - Seiden LS
LA  - eng
GR  - DA-00085/DA/NIDA NIH 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 (Serotonin Agents)
RN  - 333DO1RDJY (Serotonin)
RN  - 4H1Z7121WS (2beta-carbomethoxy-3beta-(4-iodophenyl)tropane)
RN  - I5Y540LHVR (Cocaine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Autoradiography
MH  - Brain/drug effects/metabolism
MH  - Cocaine/analogs & derivatives/metabolism
MH  - Dopamine/metabolism
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity
MH  - Radioligand Assay
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Serotonin/*metabolism
MH  - Serotonin Agents/*toxicity
MH  - Time Factors
EDAT- 1996/02/01 00:00
MHDA- 1996/02/01 00:01
CRDT- 1996/02/01 00:00
PHST- 1996/02/01 00:00 [pubmed]
PHST- 1996/02/01 00:01 [medline]
PHST- 1996/02/01 00:00 [entrez]
PST - ppublish
SO  - J Pharmacol Exp Ther. 1996 Feb;276(2):855-65.