Hippocampus-dependent learning facilitated by a monoclonal antibody or D-cycloserine.
Persistent neuronal plasticity, including that observed at some hippocampal synapses, requires N-methyl-D-aspartate (NMDA)-mediated transmission. NMDA receptor activation may be necessary for hippocampus-dependent learning as antagonists block acquisition in many such tasks. The behavioural effects of NMDA agonists are less well defined. We have shown that a monoclonal antibody (B6B21) displaced [3H]-glycine that was bound specifically to the NMDA receptor, and enhanced the opening of its integral cation channel in a glycine-like fashion, effects that were competitively antagonized by 7-chlorokynurenic acid. B6B21 also enhanced long-term potentiation in hippocampal slices. We report here that intraventricular infusions of B6B21 significantly enhances acquisition rates in hippocampus-dependent trace eye blink conditioning in rabbits, halving the number of trials required to reach a criterion of 80% conditioned responses. Peripheral injections of D-cycloserine, a partial agonist of the glycine site on the NMDA receptor which crosses the blood-brain barrier, also doubles rabbits' learning rates. Pseudoconditioning control experiments indicated a lack of nonspecific behavioural sensitization effects. Our data suggest that enhanced activation of the glycine coagonist site on the NMDA receptor/channel complex facilitates one form of associative learning and may be used in other learning tasks.
Thompson
L T
LT
Department of Cell, Molecular and Structural Biology, Northwestern University Medical School, Chicago, Illinois 60611-3008.
Moskal
J R
JR
Disterhoft
J F
JF
D000818:Animals; D000911:Antibodies, Monoclonal; D003215:Conditioning, Eyelid / Q000187:drug effects* / Q000502:physiology*; D003523:Cycloserine / Q000494:pharmacology*; D005998:Glycine / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D011817:Rabbits; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*
D000911:Antibodies, Monoclonal; D016194:Receptors, N-Methyl-D-Aspartate; D003523:Cycloserine; D005998:Glycine