L-AP4 (L-(-2-AMINO-4-PHOSPHONOBUTYRIC ACID) INDUCED IMPAIRMENT OF SPATIAL-LEARNING IN THE RAT IS ANTAGONIZED BY MAP4 ((S)-2-AMINO-2-METHYL-4-PHOSPHONOBUTANOIC ACID)())

L-AP4 an agonist at the metabotropic glutamate receptors 4, 6, 7, 8 an d 9 produced a selective spatial learning impairment in a water maze a s well as in an 8-arm maze task when injected i.c.v. (5 mu l of a 80 m M solution), a dose previously reported to block consolidation of long -term potentiation in vivo. Acquisition and recall of the spatial wate r-maze task, as measured by escape latency and quadrant bias, respecti vely, were impaired, whereas swim speed was not affected. In contrast, ability to perform a non-spatial control task was not impaired; laten cy to reach a visible escape platform was not delayed in L-AP4-treated animals. No behavioral difference was visible in the open field. MAP4 , an antagonist of mGluRs mediating L-AP4 induced reduction of transmi tter release, when administered pretraining i.c.v. (5 mu l of an 80 mM solution) did not affect motor activity in the open field test but di d impair learning of both spatial tasks. In addition, swim speed was i ncreased. However, injecting L-AP4 and MAP4 in combination at equimola r concentrations had no effect on learning in both spatial tasks or on swim speed in the water maze. Neither latency in the visible-platform test nor behavior in the open field was affected. We conclude that L- AP4 sensitive metabotropic glutamate receptors play a selective role i n learning and memory formation of the rat.