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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?

O'Callaghan MJ, Bay-Richter C, O'Tuathaigh CM, Heery DM, Waddington JL, Moran PM - J. Psychopharmacol. (Oxford) (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: School of Psychology, University of Nottingham, Nottingham, UK.

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Related in: MedlinePlus

Haloperidol (Hal) enhanced LI in both Drd–2+/+ and Drd−2-/- mice. Mean suppression ratio (SR) is shown for non-pre-exposed (NPE) and Pre-exposed groups (PE). *indicates p<0.01 significant difference from NPE group same treatment group and genotype. A high SR indicates lower suppression a low SR higher suppression.
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fig2-0269881114544774: Haloperidol (Hal) enhanced LI in both Drd–2+/+ and Drd−2-/- mice. Mean suppression ratio (SR) is shown for non-pre-exposed (NPE) and Pre-exposed groups (PE). *indicates p<0.01 significant difference from NPE group same treatment group and genotype. A high SR indicates lower suppression a low SR higher suppression.

Mentions: Haloperidol significantly potentiated LI (Figure 2). There was a significant effect of genotype [F(1,41)=6.6, p<0.05], Drug treatment [F(1,41)=9.4, p<0.05], pre-exposure [F(1,41)=38.2, p<0.0001] and a significant drug treatment × pre-exposure interaction [F(1,41)=6.1, p<0.01]. This interaction allowed us to examine the effect of drug on NPE and PE separately. There was a significant effect of drug treatment in the PE [F(1,23)=8.0, p<0.001] and not the NPE [F=.1, NS] group. There was a significant effect of pre-exposure (i.e. LI) in Haloperidol (F(1,24)=30.4, p<0.0001) but not vehicle-treated groups. There was no indication that haloperidol induction of LI was moderated in Drd−1-/- mice (drug treatment × genotype interaction [F=.22, NS]). NPE vs. PE comparisons were significant for Hal-treated groups [Drd−1+/+ T(11)=3.2, p<0.01; Drd−1-/- T(10)=15.4, p<0.001] but not vehicle-treated groups [Drd−1+/+ T(9)=0.9; Drd−1-/- T(11)=2.0, NS].


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?

O'Callaghan MJ, Bay-Richter C, O'Tuathaigh CM, Heery DM, Waddington JL, Moran PM - J. Psychopharmacol. (Oxford) (2014)

Haloperidol (Hal) enhanced LI in both Drd–2+/+ and Drd−2-/- mice. Mean suppression ratio (SR) is shown for non-pre-exposed (NPE) and Pre-exposed groups (PE). *indicates p<0.01 significant difference from NPE group same treatment group and genotype. A high SR indicates lower suppression a low SR higher suppression.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2 - License 3
Show All Figures
getmorefigures.php?uid=PMC4230883&req=5

fig2-0269881114544774: Haloperidol (Hal) enhanced LI in both Drd–2+/+ and Drd−2-/- mice. Mean suppression ratio (SR) is shown for non-pre-exposed (NPE) and Pre-exposed groups (PE). *indicates p<0.01 significant difference from NPE group same treatment group and genotype. A high SR indicates lower suppression a low SR higher suppression.
Mentions: Haloperidol significantly potentiated LI (Figure 2). There was a significant effect of genotype [F(1,41)=6.6, p<0.05], Drug treatment [F(1,41)=9.4, p<0.05], pre-exposure [F(1,41)=38.2, p<0.0001] and a significant drug treatment × pre-exposure interaction [F(1,41)=6.1, p<0.01]. This interaction allowed us to examine the effect of drug on NPE and PE separately. There was a significant effect of drug treatment in the PE [F(1,23)=8.0, p<0.001] and not the NPE [F=.1, NS] group. There was a significant effect of pre-exposure (i.e. LI) in Haloperidol (F(1,24)=30.4, p<0.0001) but not vehicle-treated groups. There was no indication that haloperidol induction of LI was moderated in Drd−1-/- mice (drug treatment × genotype interaction [F=.22, NS]). NPE vs. PE comparisons were significant for Hal-treated groups [Drd−1+/+ T(11)=3.2, p<0.01; Drd−1-/- T(10)=15.4, p<0.001] but not vehicle-treated groups [Drd−1+/+ T(9)=0.9; Drd−1-/- T(11)=2.0, NS].

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.

View Article: PubMed Central - PubMed

Affiliation: School of Psychology, University of Nottingham, Nottingham, UK.

Show MeSH
Related in: MedlinePlus