Dopamine D1 receptor involvement in latent inhibition and overshadowing

Nelson, Andrew J.D.; Thur, Karen E.; Cassaday, Helen J.

Abstract

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.

Citation

Nelson, A. J., Thur, K. E., & Cassaday, H. J. (2012). Dopamine D1 receptor involvement in latent inhibition and overshadowing. International Journal of Neuropsychopharmacology, 15(10), https://doi.org/10.1017/S1461145711001751

• Journal Article Type: Article
• Publication Date: Nov 1, 2012
• Deposit Date: Apr 17, 2014
• Publicly Available Date: Apr 17, 2014
• Journal: International Journal of Neuropsychopharmacology
• Print ISSN: 1461-1457
• Electronic ISSN: 1469-5111
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 15
• Issue: 10
• DOI: https://doi.org/10.1017/S1461145711001751
• Public URL: https://nottingham-repository.worktribe.com/output/1006345
• Publisher URL: http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=8704773&fulltextType=RA&fileId=S1461145711001751