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 metabotrophic glutamate receptors 4, 6, 7, 8 and 9 produced a selective spatial learning impairment in a water maze as well as in an 8-arm maze task when injected i.c.v. (5 microliters of a 80 mM solution), a dose previously reported to block consolidation of long-term potentiation in vivo. Acquisition and recall of the spatial water-maze task, as measured by escape latency and quadrant bias, respectively, were impaired, whereas swim speed was not affected. In contrast, ability to perform a non-spatial control task was not impaired; latency 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 transmitter release, when administered pretraining i.c.v. (5 microliters of an 80 mM solution) did not affect motor activity in the open field test but did impair learning of both spatial tasks. In addition, swim speed was increased. However, injecting L-AP4 and MAP4 in combination at equimolar 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 in learning and memory formation of the rat.
Hölscher
C
C
Department of Pharmacology and Therapeutics, Trinity College Dublin, Ireland. cholschr@mail.tcd.ie
McGlinchey
L
L
Rowan
M J
MJ
D000613:Aminobutyrates / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D017661:Receptors, Presynaptic / Q000187:drug effects
D000613:Aminobutyrates; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; D017661:Receptors, Presynaptic; C012729:2-amino-4-phosphonobutyric acid