PMID- 23384714
OWN - NLM
STAT- MEDLINE
DCOM- 20130930
LR  - 20191210
IS  - 1872-7549 (Electronic)
IS  - 0166-4328 (Linking)
VI  - 244
DP  - 2013 May 1
TI  - Effects of risperidone, clozapine and the 5-HT6 antagonist GSK-742457 on 
      PCP-induced deficits in reversal learning in the two-lever operant task in male 
      Sprague Dawley rats.
PG  - 15-28
LID - S0166-4328(13)00054-5 [pii]
LID - 10.1016/j.bbr.2013.01.035 [doi]
AB  - Reasoning and problem solving deficits have been reported in schizophrenic 
      patients. In the present study, we have tested rats in a two-lever reversal 
      learning task in a Skinner box to model these deficits. In other studies using 
      the Skinner box, atypical antipsychotics fully reversed phencyclidine 
      (PCP)-induced impairments in reversal learning which is in contrast to clinical 
      observations where antipsychotics lack the ability to fully reverse cognitive 
      deficits in schizophrenia. Therefore, it can be argued that the outcome of these 
      tests may lack predictive value. In the present study, after training on a 
      spatial discrimination between two levers, rats were exposed to a reversal of the 
      previously learned stimulus-response contingency during 5 days. We first 
      investigated the effects of sub-chronic treatment with the non-competitive 
      N-methyl-d-aspartate (NMDA) antagonists dizocilpine (MK-801) and PCP on reversal 
      learning and extinction in male Sprague Dawley rats. Subsequently, we studied the 
      effects of different PCP treatment regimes. Then, we investigated whether the 
      atypical antipsychotics risperidone and clozapine and the 5-hydroxytryptamine6 
      (5-HT6) antagonist GSK-742457 could reverse the PCP-induced deficits. All drugs 
      were administered subcutaneously (s.c.). MK-801 did not impair reversal learning, 
      while PCP (1.0 and 2.0 mg/kg) induced a clear deficit in reversal learning. Both 
      compounds, however, disrupted extinction at all tested doses. Risperidone and 
      clozapine were both ineffective in significantly ameliorating the PCP-induced 
      deficit in reversal learning which fits well with the clinical observations. The 
      lowest dose of clozapine (1.25 mg/kg) had an intermediate effect in ameliorating 
      the deficit in reversal learning induced by PCP (not different from control or 
      PCP-treated rats). The lowest dose of GSK-742457 (0.63 mg/kg) fully reversed the 
      PCP-induced deficits while the higher dose (5.0 mg/kg) had an intermediate 
      effect.
CI  - Copyright (c) 2013 Elsevier B.V. All rights reserved.
FAU - de Bruin, N M W J
AU  - de Bruin NM
AD  - Abbott Healthcare Products BV (Formerly Solvay Pharmaceuticals BV), C.J. van 
      Houtenlaan 36, 1381 CP Weesp, The Netherlands. Natasja.Debruin@ime.fraunhofer.de
FAU - van Drimmelen, M
AU  - van Drimmelen M
FAU - Kops, M
AU  - Kops M
FAU - van Elk, J
AU  - van Elk J
FAU - Wetering, M Middelveld-van de
AU  - Wetering MM
FAU - Schwienbacher, I
AU  - Schwienbacher I
LA  - eng
PT  - Journal Article
DEP - 20130204
PL  - Netherlands
TA  - Behav Brain Res
JT  - Behavioural brain research
JID - 8004872
RN  - 0 (3-benzenesulfonyl-8-piperazin-1-ylquinoline)
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Quinolines)
RN  - 0 (Serotonin Antagonists)
RN  - 0 (Sulfones)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - J1DOI7UV76 (Phencyclidine)
RN  - J60AR2IKIC (Clozapine)
RN  - L6UH7ZF8HC (Risperidone)
SB  - IM
MH  - Animals
MH  - Antipsychotic Agents/pharmacology
MH  - Clozapine/*pharmacology
MH  - Conditioning, Operant/*drug effects
MH  - Dizocilpine Maleate/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Extinction, Psychological/drug effects
MH  - Learning Disabilities/chemically induced
MH  - Male
MH  - Phencyclidine/antagonists & inhibitors/*pharmacology
MH  - Quinolines/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reversal Learning/*drug effects
MH  - Risperidone/*pharmacology
MH  - Serotonin Antagonists/pharmacology
MH  - Sulfones/*pharmacology
EDAT- 2013/02/07 06:00
MHDA- 2013/10/01 06:00
CRDT- 2013/02/07 06:00
PHST- 2012/11/17 00:00 [received]
PHST- 2013/01/21 00:00 [revised]
PHST- 2013/01/26 00:00 [accepted]
PHST- 2013/02/07 06:00 [entrez]
PHST- 2013/02/07 06:00 [pubmed]
PHST- 2013/10/01 06:00 [medline]
AID - S0166-4328(13)00054-5 [pii]
AID - 10.1016/j.bbr.2013.01.035 [doi]
PST - ppublish
SO  - Behav Brain Res. 2013 May 1;244:15-28. doi: 10.1016/j.bbr.2013.01.035. Epub 2013 
      Feb 4.