PMID- 1425989
OWN - NLM
STAT- MEDLINE
DCOM- 19921201
LR  - 20190624
IS  - 0014-2999 (Print)
IS  - 0014-2999 (Linking)
VI  - 220
IP  - 2-3
DP  - 1992 Sep 22
TI  - The 5-HT2 receptor antagonist, MDL 28,133A, disrupts the 
      serotonergic-dopaminergic interaction mediating the neurochemical effects of 
      3,4-methylenedioxymethamphetamine.
PG  - 151-9
AB  - The selective 5-HT2 receptor antagonist MDL 28,133A dose dependently-blocked the 
      long-term deficits in rat brain 5-HT concentrations produced by the substituted 
      amphetamine analogue 3,4-methylenedioxymethamphetamine (MDMA). This protective 
      effect of MDL 28,133A could be abolished by coadministration of the dopamine 
      precursor, L-dihydroxyphenylalanine (L-DOPA). Electrophysiological experiments 
      demonstrated that the ability of MDL 28,133A to block the MDMA-induced slowing of 
      A9 dopaminergic neurons was also sensitive to L-DOPA administration. Both sets of 
      experiments suggest an interaction of MDL 28,133A at the level of dopamine 
      synthesis. Consistent with this explanation, MDL 28,133A antagonized the 
      MDMA-induced stimulation of dopamine synthesis in vivo. MDMA-induced 5-HT release 
      did not reduce the firing rate of dopaminergic neurons as assessed by dopamine 
      depletion following synthesis inhibition with alpha-methyl-p-tyrosine 
      (alpha-MPT). This indicates that the effect of 5-HT2 receptor antagonists on 
      MDMA-induced dopamine synthesis is not due simply to the removal of an inhibitory 
      serotonergic input followed by an increase in dopamine cell firing and 
      autoreceptor activation. MDL 28,133A was also shown to be without effect on the 
      sensitivity of terminal dopamine autoreceptors. The results are consistent with 
      the hypothesis that 5-HT2 receptors are permissive for the stimulation of 
      dopamine synthesis necessary to support MDMA-induced transmitter efflux.
FAU - Schmidt, C J
AU  - Schmidt CJ
AD  - Marion Merrell Dow Research Institute, Cincinnati, OH 45215.
FAU - Black, C K
AU  - Black CK
FAU - Taylor, V L
AU  - Taylor VL
FAU - Fadayel, G M
AU  - Fadayel GM
FAU - Humphreys, T M
AU  - Humphreys TM
FAU - Nieduzak, T R
AU  - Nieduzak TR
FAU - Sorensen, S M
AU  - Sorensen SM
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Methyltyrosines)
RN  - 0 (Piperidines)
RN  - 0 (Receptors, Serotonin)
RN  - 0 (Serotonin Antagonists)
RN  - 136861-96-6 (MDL 28133A)
RN  - 333DO1RDJY (Serotonin)
RN  - 46627O600J (Levodopa)
RN  - 4764-17-4 (3,4-Methylenedioxyamphetamine)
RN  - 658-48-0 (alpha-Methyltyrosine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - 3,4-Methylenedioxyamphetamine/*pharmacology
MH  - Animals
MH  - Brain/*drug effects/metabolism
MH  - Corpus Striatum/drug effects/metabolism
MH  - Dopamine/biosynthesis/*metabolism
MH  - Electrophysiology
MH  - Levodopa/pharmacology
MH  - Male
MH  - Methyltyrosines/pharmacology
MH  - Neurons/drug effects/metabolism
MH  - Piperidines/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Serotonin/drug effects/metabolism
MH  - Serotonin/*metabolism
MH  - Serotonin Antagonists/*pharmacology
MH  - alpha-Methyltyrosine
EDAT- 1992/09/22 00:00
MHDA- 1992/09/22 00:01
CRDT- 1992/09/22 00:00
PHST- 1992/09/22 00:00 [pubmed]
PHST- 1992/09/22 00:01 [medline]
PHST- 1992/09/22 00:00 [entrez]
AID - 0014-2999(92)90743-N [pii]
AID - 10.1016/0014-2999(92)90743-n [doi]
PST - ppublish
SO  - Eur J Pharmacol. 1992 Sep 22;220(2-3):151-9. doi: 10.1016/0014-2999(92)90743-n.