Dopaminergic agonists impair latent learning in mice: possible modulation by noradrenergic function

K Ichihara, T Nabeshima and T Kameyama

Department of Chemical Pharmacology, Faculty of Pharmaceutical Science, Meijo University, Nagoya, Japan.

The effects of the dopamine agonists apomorphine, GBR-12909, nomifensine and methamphetamine on latent learning were investigated using a one-trial, water-finding task in mice. Mice without water deprivation were given these agonists or their vehicle before a training trial which consisted of exposure to a novel open-field environment containing a water tube. Twenty-four hours later and after 20 hr of water deprivation, animals were placed in the same apparatus and tested for the time required to find the water tube. Vehicle control animals exposed to the training trial demonstrated latent learning as measured by a significantly shorter time taken to find the water tube during the test trial as compared with naive controls that had not been exposed to the training trial. All of the dopamine agonists impaired the development of latent learning. The effects of nomifensine and methamphetamine were relatively weaker than those of apomorphine and GBR-12909. (-)-Sulpiride, a dopamine D2 antagonist, counteracted the disruptive effect of apomorphine on latent learning, whereas SCH 23390, a dopamine D1 antagonist, did not. The noradrenaline uptake inhibitor desipramine had no significant effect on latent learning. The disruptive effect of GBR-12909 on latent learning was significantly reduced when desipramine was given concurrently. Moreover, noradrenaline depletion with the neurotoxin, DSP4, impeded latent learning. These results suggest that activation of dopaminergic systems by dopamine agonists suppresses acquisition of latent learning. The qualitative and quantitative differences in the effects produced by the various agonists may be associated with their effects on noradrenergic transmission.

Volume 264, Issue 1, pp. 122-128, 01/01/1993
Copyright © 1993 by American Society for Pharmacology and Experimental Therapeutics

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