PMID- 8935805
OWN - NLM
STAT- MEDLINE
DCOM- 19970129
LR  - 20190726
IS  - 0033-3158 (Print)
IS  - 0033-3158 (Linking)
VI  - 124
IP  - 1-2
DP  - 1996 Mar
TI  - 5-HT modulation of auditory and visual sensorimotor gating: II. Effects of the 
      5-HT2A antagonist MDL 100,907 on disruption of sound and light prepulse 
      inhibition produced by 5-HT agonists in Wistar rats.
PG  - 107-16
AB  - Increasing evidence suggests an important role of 5-HT, and 5-HT2A receptors in 
      particular, in the etiology and treatment of schizophrenia. The prepulse 
      inhibition paradigm is used as a model for sensorimotor gating processes that are 
      disrupted in schizophrenia. The present study used the selective serotonin2A 
      (5-HT2A) antagonist and putative antipsychotic agent MDL 100,907 to evaluate the 
      contribution of 5-HT2A receptors to the disruptions of prepulse inhibition 
      produced by several 5-HT agonists. The D2 antagonist haloperidol was used to 
      evaluate a possible interaction with dopamine neurons. Sound or light prepulses 
      were used to measure the generality of these drug effects on cross-modal prepulse 
      inhibition. In the first study, MDL 100,907 antagonized the disruptions of 
      auditory prepulse inhibition produced by the 5-HT releasing agents fenfluramine 
      and 3,4-methylenedioxymethamphetamine (MDMA). These effects on prepulse 
      inhibition were modality-specific in that MDL 100,907 did not reverse the effects 
      of the 5-HT releasers on visual prepulse inhibition. Haloperidol did not alter 
      the disruptive effects of MDMA or fenfluramine on either auditory or visual 
      prepulse inhibition. In the second study, the direct acting 5-HT2A/2C receptor 
      agonist/hallucinogen (+)1-4-iodo-2,5-dimethoxyphenyl-2-aminopropane (DOI) 
      consistently disrupted auditory prepulse inhibition, and this effect was blocked 
      by MDL 100,907 but not by haloperidol. A dose-response analysis demonstrated that 
      MDL 100,907 potently antagonized DOI disrupted auditory prepulse inhibition, with 
      an ED50 of 0.04 mg/kg, IP. DOI did not consistently disrupt visual prepulse 
      inhibition. In summary, these data indicate that, at least under the conditions 
      of the present studies, the disruptions of auditory prepulse inhibition produced 
      by fenfluramine, MDMA, and DOI result from stimulation of 5-HT2A receptors. 
      Furthermore, these disruptions do not involve direct or indirect stimulation of 
      D2 receptors. The identity of the 5-HT receptor(s) underlying the disruptive 
      effects of fenfluramine or MDMA on visual prepulse inhibition has not yet been 
      identified. MDL 100,907 may be generally useful in CNS disorders in which 
      excessive 5-HT2A receptor tone disrupts sensory gating processes.
FAU - Padich, R A
AU  - Padich RA
AD  - Hoechst Marion Roussel Inc., Cincinnati, OH 45215, USA.
FAU - McCloskey, T C
AU  - McCloskey TC
FAU - Kehne, J H
AU  - Kehne JH
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (Amphetamines)
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Fluorobenzenes)
RN  - 0 (Piperidines)
RN  - 0 (Receptor, Serotonin, 5-HT2A)
RN  - 0 (Receptors, Serotonin)
RN  - 0 (Serotonin Receptor Agonists)
RN  - 2DS058H2CF (Fenfluramine)
RN  - EW71EE171J (volinanserin)
RN  - J6292F8L3D (Haloperidol)
RN  - OOM10GW9UE (4-iodo-2,5-dimethoxyphenylisopropylamine)
SB  - IM
MH  - Amphetamines/pharmacology
MH  - Animals
MH  - Antipsychotic Agents/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Fenfluramine/pharmacology
MH  - Fluorobenzenes/*pharmacology
MH  - Haloperidol/pharmacology
MH  - Male
MH  - Piperidines/*pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, Serotonin, 5-HT2A
MH  - Receptors, Serotonin/*drug effects
MH  - Reflex, Startle/*drug effects
MH  - Serotonin Receptor Agonists/*pharmacology
EDAT- 1996/03/01 00:00
MHDA- 1996/03/01 00:01
CRDT- 1996/03/01 00:00
PHST- 1996/03/01 00:00 [pubmed]
PHST- 1996/03/01 00:01 [medline]
PHST- 1996/03/01 00:00 [entrez]
AID - 10.1007/BF02245610 [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 1996 Mar;124(1-2):107-16. doi: 10.1007/BF02245610.