TY - JOUR
T1 - Disruption and potentiation of latent inhibition by risperidone
T2 - The latent inhibition model of atypicalantipsychotic action
AU - Weiner, Ina
AU - Schiller, Daniela
AU - Gaisler-Salomon, Inna
PY - 2003/3
Y1 - 2003/3
N2 - Latent Inhibition (LI), that is, retarded conditioning to a Stimulus following its nonreinforced pre-exposure, is impaired in some subsets of schizophrenia patients and in amphetamine-treated rats. Potentiation of LI by antipsychotic drugs (APDs) given in conditioning, underconditions that do not lead to LI in controls, is a well-established index of antipsychotic activity. Recently, we have shown that the atypicalAPD, clozapine, in addition disrupts LI if administered in pre-exposure, under conditions that lead to LI in controls. This studydemonstrates the same behavioralprofilefortheatypicalAPDrisperidone. LI was measured in a thirst-motivated conditioned emotionalresponse procedure by comparing suppression of drinking in response to atone previously paired with afoot shock in rats that receivednonreinforced exposure to the tone priorto conditioning (pre-exposed (PE)) and rats for whom the tone was novel(non-pre-exposed(NPE)). We show that under conditions that did not yield LI in vehicle controls (40 pre-exposures and five conditioning trials), risperidone (0.25, 0.5, and 1.2 mg/kg) led to LI when administered in conditioning. Under conditions that led to LI in vehicle controls (40pre-exposures and two conditioning trials), risperidone (0.25, 0.5, and 2.5 mg/kg) abolished LI when administered in pre-exposure; thelatter effect was not evident with haloperidol. In addition, the effects of risperidone administered in both the pre-exposure andconditioning stages were dose-dependent so that the pre-exposure-based action was manifested at lower but not at higher doses. It isconcluded that atypicalAPDs exert in the LI modeladualpattern of effects, which enables detection of their ‘typical' action(conditioning-based LI potentiation) as wellasa dissociation from typicalAPDs by their ‘atypical' action (pre-exposure-based LIdisruption). It is suggested that the former and latter effects are subserved by D2 and 5HT2A antagonism, respectively.
AB - Latent Inhibition (LI), that is, retarded conditioning to a Stimulus following its nonreinforced pre-exposure, is impaired in some subsets of schizophrenia patients and in amphetamine-treated rats. Potentiation of LI by antipsychotic drugs (APDs) given in conditioning, underconditions that do not lead to LI in controls, is a well-established index of antipsychotic activity. Recently, we have shown that the atypicalAPD, clozapine, in addition disrupts LI if administered in pre-exposure, under conditions that lead to LI in controls. This studydemonstrates the same behavioralprofilefortheatypicalAPDrisperidone. LI was measured in a thirst-motivated conditioned emotionalresponse procedure by comparing suppression of drinking in response to atone previously paired with afoot shock in rats that receivednonreinforced exposure to the tone priorto conditioning (pre-exposed (PE)) and rats for whom the tone was novel(non-pre-exposed(NPE)). We show that under conditions that did not yield LI in vehicle controls (40 pre-exposures and five conditioning trials), risperidone (0.25, 0.5, and 1.2 mg/kg) led to LI when administered in conditioning. Under conditions that led to LI in vehicle controls (40pre-exposures and two conditioning trials), risperidone (0.25, 0.5, and 2.5 mg/kg) abolished LI when administered in pre-exposure; thelatter effect was not evident with haloperidol. In addition, the effects of risperidone administered in both the pre-exposure andconditioning stages were dose-dependent so that the pre-exposure-based action was manifested at lower but not at higher doses. It isconcluded that atypicalAPDs exert in the LI modeladualpattern of effects, which enables detection of their ‘typical' action(conditioning-based LI potentiation) as wellasa dissociation from typicalAPDs by their ‘atypical' action (pre-exposure-based LIdisruption). It is suggested that the former and latter effects are subserved by D2 and 5HT2A antagonism, respectively.
KW - Atypicalantipsychotic drugs
KW - Haloperidol
KW - Latent inhibition
KW - Rat
KW - Risperidone
KW - Schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=0038323855&partnerID=8YFLogxK
U2 - 10.1038/sj.npp.1300069
DO - 10.1038/sj.npp.1300069
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AN - SCOPUS:0038323855
SN - 0893-133X
VL - 28
SP - 499
EP - 509
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 3
ER -