Dopamine D1 receptor involvement in latent inhibition and overshadowing

Latent inhibition (LI) manifests as poorer conditioning to a stimulus that has previously been experienced without consequence. There is good evidence of dopaminergic modulation of LI, as the effect is reliably disrupted by the indirect dopamine (DA) agonist amphetamine. The disruptive effects of am...

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Main Authors: Nelson, Andrew J.D., Thur, Karen E., Cassaday, Helen J.
Format: Article
Published: Cambridge University Press 2012
Online Access:https://eprints.nottingham.ac.uk/2520/
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author Nelson, Andrew J.D.
Thur, Karen E.
Cassaday, Helen J.
author_facet Nelson, Andrew J.D.
Thur, Karen E.
Cassaday, Helen J.
author_sort Nelson, Andrew J.D.
building Nottingham Research Data Repository
collection Online Access
description Latent inhibition (LI) manifests as poorer conditioning to a stimulus that has previously been experienced without consequence. There is good evidence of dopaminergic modulation of LI, as the effect is reliably disrupted by the indirect dopamine (DA) agonist amphetamine. The disruptive effects of amphetamine on LI are reversed by both typical and atypical antipsychotics, which on their own are able to facilitate LI. However, the contribution of different DA receptors to these effects is poorly understood. Amphetamine effects on another stimulus selection procedure, overshadowing, have been suggested to be D1-mediated. Thus, in the current experiments, we systematically investigated the role of D1 receptors in LI. First, we tested the ability of the full D1 agonist SKF 81297 to abolish LI and compared the effects of this drug on LI and overshadowing. Subsequently, we examined whether the D1 antagonist SCH 23390 can lead to the emergence of LI under conditions that do not produce the effect in normal animals (weak pre-exposure). Finally, we tested the ability of SCH 23390 to block amphetamine-induced disruption of LI. We found little evidence that direct stimulation of D1 receptors abolishes LI (although there was some attenuation of LI at 0.4 mg/kg SKF 81297). Similarly, SCH 23390 failed to enhance LI. However, SCH 23390 did block amphetamine-induced disruption of LI. These data indicate that, while LI may be unaffected by selective manipulation of activity at D1 receptors, the effects of amphetamine on LI are to some extent dependent on actions at D1 receptors.
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spelling nottingham-25202020-05-04T20:21:15Z https://eprints.nottingham.ac.uk/2520/ Dopamine D1 receptor involvement in latent inhibition and overshadowing Nelson, Andrew J.D. Thur, Karen E. Cassaday, Helen J. Latent inhibition (LI) manifests as poorer conditioning to a stimulus that has previously been experienced without consequence. There is good evidence of dopaminergic modulation of LI, as the effect is reliably disrupted by the indirect dopamine (DA) agonist amphetamine. The disruptive effects of amphetamine on LI are reversed by both typical and atypical antipsychotics, which on their own are able to facilitate LI. However, the contribution of different DA receptors to these effects is poorly understood. Amphetamine effects on another stimulus selection procedure, overshadowing, have been suggested to be D1-mediated. Thus, in the current experiments, we systematically investigated the role of D1 receptors in LI. First, we tested the ability of the full D1 agonist SKF 81297 to abolish LI and compared the effects of this drug on LI and overshadowing. Subsequently, we examined whether the D1 antagonist SCH 23390 can lead to the emergence of LI under conditions that do not produce the effect in normal animals (weak pre-exposure). Finally, we tested the ability of SCH 23390 to block amphetamine-induced disruption of LI. We found little evidence that direct stimulation of D1 receptors abolishes LI (although there was some attenuation of LI at 0.4 mg/kg SKF 81297). Similarly, SCH 23390 failed to enhance LI. However, SCH 23390 did block amphetamine-induced disruption of LI. These data indicate that, while LI may be unaffected by selective manipulation of activity at D1 receptors, the effects of amphetamine on LI are to some extent dependent on actions at D1 receptors. Cambridge University Press 2012-11 Article PeerReviewed Nelson, Andrew J.D., Thur, Karen E. and Cassaday, Helen J. (2012) Dopamine D1 receptor involvement in latent inhibition and overshadowing. International Journal of Neuropsychopharmacology, 15 (10). pp. 1513-1523. ISSN 1461-1457 http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=8704773&fulltextType=RA&fileId=S1461145711001751 doi:10.1017/S1461145711001751 doi:10.1017/S1461145711001751
spellingShingle Nelson, Andrew J.D.
Thur, Karen E.
Cassaday, Helen J.
Dopamine D1 receptor involvement in latent inhibition and overshadowing
title Dopamine D1 receptor involvement in latent inhibition and overshadowing
title_full Dopamine D1 receptor involvement in latent inhibition and overshadowing
title_fullStr Dopamine D1 receptor involvement in latent inhibition and overshadowing
title_full_unstemmed Dopamine D1 receptor involvement in latent inhibition and overshadowing
title_short Dopamine D1 receptor involvement in latent inhibition and overshadowing
title_sort dopamine d1 receptor involvement in latent inhibition and overshadowing
url https://eprints.nottingham.ac.uk/2520/
https://eprints.nottingham.ac.uk/2520/
https://eprints.nottingham.ac.uk/2520/