NMDA receptor activity in learning spatial procedural strategies: II. The influence of cerebellar lesions

Experimental data support the involvement of cerebellar circuits in the acquisition of spatial procedural competences. Since the ability to acquire new procedural competences is lost when cerebellar regions are lesioned or when NMDA receptor activity is blocked, we analyzed whether the learning of explorative strategies is affected by blocking NMDA receptor activity in the presence of cerebellar lesions. To this aim, the NMDA receptor antagonist (CGS 19755, 7 mg/kg) was administered i.p. to un-lesioned rats, or rats subjected to total ablation of the cerebellum or to hemi-cerebellectomy. CGS 19755 and cerebellectomy both produced water maze behavior characterized by circling. Administration of CGS 19755 did not modify the Morris Water Maze (MWM) peripheral circling behavior of cerebellectomized animals. Circling was the dominant strategy of hemicerebellectomized animals in the absence of drugs. However, increasingly compulsive circling was observed under the action of CGS 19755. Circling was not observed if the drug-treated animals (un-lesioned or lesioned) had been previously trained. In conclusion, the NMDA antagonist caused severe impairment in the acquisition of spatial procedures, thus mimicking the consequences of cerebellar ablation on spatial procedural learning. Based on the present findings, we hypothesize that cerebellar NMDA receptor activity is involved in the acquisition of procedural spatial competence.