PMID- 8099482
OWN - NLM
STAT- MEDLINE
DCOM- 19930712
LR  - 20181130
IS  - 0893-133X (Print)
IS  - 0893-133X (Linking)
VI  - 8
IP  - 3
DP  - 1993 May
TI  - Serotonin1B receptor activation mimics behavioral effects of presynaptic 
      serotonin release.
PG  - 201-11
AB  - The locomotor hyperactivity induced by 3,4-methylene-dioxymethamphetamine (MDMA) 
      and related drugs in rats appears to be due to the drug-induced release of 
      presynaptic serotonin (5-HT). Thus, these drugs increase locomotor activity by 
      acting as indirect 5-HT agonists. The subtype of 5-HT receptor upon which this 
      released 5-HT acts postsynaptically to produce the activating effect of MDMA-like 
      drugs is not known. When tested under conditions in which MDMA increases 
      locomotion, direct agonists at both 5-HT1A and 5-HT1C/2 receptors consistently 
      decrease locomotion. Hence, the present experiments tested the hypothesis that 
      the hyperactivity produced by the release of endogenous 5-HT is due to the 
      activation of 5-HT1B receptors. Using the Behavioral Pattern Monitor (BPM), the 
      profile of behavioral effects of a 5-HT1B agonist, 
      5-methoxy-3(1,2,3,6)tetrahydropyridin-4yl)-1H-indole (RU 24969), was compared to 
      that previously described for MDMA and related indirect 5-HT agonists. The BPM 
      provided detailed information regarding the amount and qualitative patterning of 
      locomotor activity and investigatory responses in rats. Various doses of RU 24969 
      (1.25 to 5 mg/kg) were administered to naive male rats 10 minutes prior to 
      placement in the test chambers. As previously reported for MDMA, locomotor 
      activity increased with dose, and investigatory rearings and holepokes decreased. 
      The hyperactivity was characterized by repetitive spatial patterns of locomotion 
      that were qualitatively similar to those produced by indirect 5-HT agonists such 
      as MDMA and dissimilar to those produced by indirect dopamine (DA) agonists such 
      as amphetamine. Pretreatment with racemic propranolol but not (+)propranolol 
      antagonized the hyperactivity induced by RU 24959. Fluoxetine, a 5-HT reuptake 
      inhibitor, failed to block the locomotor activating effects of RU 24969. These 
      findings confirm the similarity between the behavioral effects of RU 24969 and 
      indirect 5-HT agonists and suggest that the locomotor hyperactivity produced by 
      both RU 24969 and MDMA is mediated by the activation of 5-HT1B receptors. 
      Although the effects of MDMA on 5-HT1B receptors are secondary to its ability to 
      release presynaptic 5-HT, the activation produced by RU 24969 appears to be a 
      consequence of its direct agonist effects.
FAU - Rempel, N L
AU  - Rempel NL
AD  - Department of Psychiatry, School of Medicine, University of California, San 
      Diego, La Jolla 92093-0804.
FAU - Callaway, C W
AU  - Callaway CW
FAU - Geyer, M A
AU  - Geyer MA
LA  - eng
GR  - DA02925/DA/NIDA NIH HHS/United States
GR  - DA06325/DA/NIDA NIH HHS/United States
GR  - MH00188/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - 0 (Designer Drugs)
RN  - 0 (Dopamine Agents)
RN  - 0 (Indoles)
RN  - 0 (Receptors, Serotonin)
RN  - 0 (Serotonin Receptor Agonists)
RN  - 01K63SUP8D (Fluoxetine)
RN  - 2ISE72RACC (5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole)
RN  - 333DO1RDJY (Serotonin)
RN  - 3G6A5W338E (Caffeine)
RN  - 4764-17-4 (3,4-Methylenedioxyamphetamine)
RN  - 6M3C89ZY6R (Nicotine)
RN  - 9Y8NXQ24VQ (Propranolol)
RN  - DL48G20X8X (Scopolamine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - 3,4-Methylenedioxyamphetamine/analogs & derivatives/pharmacology
MH  - Animals
MH  - Behavior, Animal/drug effects/*physiology
MH  - Caffeine/pharmacology
MH  - Designer Drugs/pharmacology
MH  - Dopamine Agents/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Fluoxetine/pharmacology
MH  - Indoles/*pharmacology
MH  - Male
MH  - Motor Activity/drug effects
MH  - N-Methyl-3,4-methylenedioxyamphetamine
MH  - Nicotine/pharmacology
MH  - Propranolol/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Serotonin/*drug effects
MH  - Scopolamine/pharmacology
MH  - Serotonin/*metabolism
MH  - Serotonin Receptor Agonists/*pharmacology
MH  - Synapses/drug effects/*metabolism
EDAT- 1993/05/01 00:00
MHDA- 1993/05/01 00:01
CRDT- 1993/05/01 00:00
PHST- 1993/05/01 00:00 [pubmed]
PHST- 1993/05/01 00:01 [medline]
PHST- 1993/05/01 00:00 [entrez]
AID - 10.1038/npp.1993.22 [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 1993 May;8(3):201-11. doi: 10.1038/npp.1993.22.