PMID- 15953492
OWN - NLM
STAT- MEDLINE
DCOM- 20050802
LR  - 20191210
IS  - 0006-3223 (Print)
IS  - 0006-3223 (Linking)
VI  - 57
IP  - 12
DP  - 2005 Jun 15
TI  - Kappa opioid receptor activation disrupts prepulse inhibition of the acoustic 
      startle in rats.
PG  - 1550-8
AB  - BACKGROUND: Compelling evidence indicates that kappa opioid receptor (KOR) 
      agonists produce perceptual distortions in animals and humans, yet the mechanism 
      of action and clinical relevance of such effects remain unclear. Since 
      abnormalities in preattentional functions and informational processing are 
      hypothesized to underlie psychotic disorders, the present study has been designed 
      to assess the role of KOR on sensorimotor gating. METHODS: The effects of the 
      selective KOR agonist U50488 were evaluated on the behavioral paradigm of 
      prepulse inhibition (PPI) of the acoustic startle reflex (ASR). RESULTS: U50488 
      (1.25, 2.5, and 5 mg/kg, subcutaneous [SC]) induced a dose-dependent reduction of 
      PPI, which was efficiently prevented by the selective KOR antagonist 
      norbinaltorphimine (nor-BNI, 10 mg/kg, SC), as well as by the atypical 
      antipsychotic clozapine (5, 8 mg/kg, intraperitoneal [IP]) but not by the typical 
      antipsychotic haloperidol (.1, .5 mg/kg, IP). Conversely, nor-BNI (10 mg/kg, SC) 
      failed to reverse the PPI disruption mediated by both apomorphine (.25 mg/kg, SC) 
      and dizocilpine (.1 mg/kg, SC). CONCLUSIONS: Our results support a pivotal role 
      of KOR in the regulation of preattentional functions and sensorimotor gating, 
      pointing to these receptors as a possible neurobiological substrate especially 
      relevant to the clusters of psychosis unresponsive to typical antipsychotics.
FAU - Bortolato, Marco
AU  - Bortolato M
AD  - Department of Psychiatry and Human Behavior, University of California, Irvine, 
      California, USA. bortolam@uci.edu
FAU - Aru, Gian Nicola
AU  - Aru GN
FAU - Frau, Roberto
AU  - Frau R
FAU - Orru, Marco
AU  - Orru M
FAU - Fa, Mauro
AU  - Fa M
FAU - Manunta, Mario
AU  - Manunta M
FAU - Puddu, Mara
AU  - Puddu M
FAU - Mereu, Giampaolo
AU  - Mereu G
FAU - Gessa, Gian Luigi
AU  - Gessa GL
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Biol Psychiatry
JT  - Biological psychiatry
JID - 0213264
RN  - 0 (Analgesics, Non-Narcotic)
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Dopamine Agonists)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Narcotic Antagonists)
RN  - 0 (Receptors, Opioid, kappa)
RN  - 36OOQ86QM1 (norbinaltorphimine)
RN  - 5S6W795CQM (Naltrexone)
RN  - 67198-13-4 
      (3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, 
      (trans)-Isomer)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - J60AR2IKIC (Clozapine)
RN  - J6292F8L3D (Haloperidol)
RN  - N21FAR7B4S (Apomorphine)
SB  - IM
MH  - 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, 
      (trans)-Isomer/pharmacology
MH  - Acoustic Stimulation/*methods
MH  - Analgesics, Non-Narcotic/pharmacology
MH  - Analysis of Variance
MH  - Animals
MH  - Antipsychotic Agents/pharmacology
MH  - Apomorphine/pharmacology
MH  - Clozapine/pharmacology
MH  - Dizocilpine Maleate/pharmacology
MH  - Dopamine Agonists/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Dose-Response Relationship, Radiation
MH  - Drug Interactions
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Haloperidol/pharmacology
MH  - *Inhibition, Psychological
MH  - Male
MH  - Naltrexone/*analogs & derivatives/pharmacology
MH  - Narcotic Antagonists/pharmacology
MH  - Rats
MH  - Receptors, Opioid, kappa/*physiology
MH  - Reflex, Startle/drug effects/*physiology
EDAT- 2005/06/15 09:00
MHDA- 2005/08/03 09:00
CRDT- 2005/06/15 09:00
PHST- 2004/11/24 00:00 [received]
PHST- 2005/02/09 00:00 [revised]
PHST- 2005/02/18 00:00 [accepted]
PHST- 2005/06/15 09:00 [pubmed]
PHST- 2005/08/03 09:00 [medline]
PHST- 2005/06/15 09:00 [entrez]
AID - S0006-3223(05)00236-2 [pii]
AID - 10.1016/j.biopsych.2005.02.030 [doi]
PST - ppublish
SO  - Biol Psychiatry. 2005 Jun 15;57(12):1550-8. doi: 10.1016/j.biopsych.2005.02.030.