Potentiation of latent inhibition by haloperidol and clozapine is attenuated in Dopamine D2 receptor (Drd-2)-deficient mice: do antipsychotics influence learning to ignore irrelevant stimuli via both Drd-2 and non-Drd-2 mechanisms?
Bottom Line: Whether the dopamine Drd-2 receptor is necessary for the behavioural action of antipsychotic drugs is an important question, as Drd-2 antagonism is responsible for their debilitating motor side effects.These data suggest that antipsychotic drugs can have either Drd-2 or non-Drd-2 effects on learning to ignore irrelevant stimuli, depending on how the abnormality is produced.Identification of the non-Drd-2 mechanism may help to identify novel non-Drd2 based therapeutic strategies for psychosis.
Affiliation: School of Psychology, University of Nottingham, Nottingham, UK.Show MeSH
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Mentions: Both clozapine and haloperidol potentiated LI in Drd−2+/+ but not in Drd−2-/- (Figure 1(a)). In a three-way ANOVA (pre-exposure × drug treatment × genotype) there was a significant effect of pre-exposure [F(1,70)=60.3, p<0.001] and drug treatment [F(1,70)=7.35, p<0.001], and pre-exposure × drug treatment [F(2,70)=6.21, p<0.005] and genotype × drug treatment interactions [F(2,70)=4.49, p<0.05]. There was a significant effect of drug treatment in Drd−2+/+ mice [F(2,34)=24.8, p<0.0001] but not in Drd−2-/- [F(2,36)=0.1, NS]. The three-way pre-exposure × genotype × drug treatment interaction was significant [F(2,70)=4.2, p<0.05], therefore drug, genotype and pre-exposure were analysed separately for post hoc comparisons. Vehicle-treated (Veh) Drd–2+/+ mice receiving a low number of pre-exposures did not show LI [NPE vs. PE T10=.24] while clozapine [NPE vs. PE T11=18.8, p<0.0001]- and haloperidol [NPE vs. PE T14=5.9, p<0.0001]-treated Drd−2+/+ mice do. NPE vs. PE was not significant for any drug groups in Drd−2-/- mice following correction, but Veh and Clozapine groups had uncorrected p-values of <0.05. Further support for differences between genotypes is provided by comparison of drug treated PE groups for each genotype; Veh vs. Hal [Drd−2+/+ T12=6.47, p<0.001; Drd−2-/- T13=.25, NS]. Veh vs. Clozapine [Drd−2+/+ T9=21.3, p<0. 0001; Drd−2-/- T15=.5, NS].
Affiliation: School of Psychology, University of Nottingham, Nottingham, UK.