Effects of the selective dopamine D1 antagonists NNC 01-0112 and SCH 39166 on latent inhibition in the rat

Add time:08/28/2019    Source:sciencedirect.com

Dopamine D1 receptor blockade does not appear to be a prerequisite for antipsychotic activity since many clinically effective antipsychotics have little or no affinity for this receptor subtype. Clozapine, however, which has minimal liability for extrapyramidal symptoms, possesses affinities of similar order for D1 and D2 receptors. In earlier animal models used to predict antipsychotic effect, selective D1 antagonists have shown effects similar to standard antipsychotics with preferential D2 or mixed D1/D2 antagonism. We investigated the effects of haloperidol (0.1 mg/kg) and two selective D1 antagonists, NNC 01-0112 (0.05, 0.1 and 0.2 mg/kg) and SCH 39166 (0.02, 0.2 and 2.0 mg/kg), on latent inhibition (LI) in rats. LI is a behavioural paradigm in which repeated nonreinforced preexposure to a stimulus retards subsequent associations to that stimulus. Disrupted LI has been suggested as a model for the attentional deficits in schizophrenia. Using preexposure to a flashing light stimulus, which subsequently served as a conditioned stimulus for suppression of water licking, we demonstrated a clear LI effect with haloperidol but with neither of the two D1 antagonists. Since selective D1 antagonists are not clinically effective, these results add further credibility for the relevance of LI as an animal model of psychosis.

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