M. Pitkanen et al., D-CYCLOSERINE, A PARTIAL AGONIST AT THE GLYCINE SITE, ENHANCES THE EXCITABILITY OF DENTATE GRANULE CELLS IN-VIVO IN RATS, European journal of pharmacology, 253(1-2), 1994, pp. 125-129
The present study investigated the dose-dependent effects of d-cyclose
rine, a partial agonist at the glycine modulatory site associated with
the NMDA receptor complex. on the hippocampal field potentials of den
tate granule cells in awake, freely moving rats. Five sequential field
potentials were recorded from the dentate gyrus of the dorsal hippoca
mpus, by stimulating the perforant path in the entorhinal cortex at 30
-s intervals. The slope of the population excitatory postsynaptic pote
ntial (e.p.s.p.) and the amplitude of the population spike of these fi
eld potentials were analysed and averaged with a computer. The effects
of d-cycloserine (1.0, 3.0, 9.0 mg/kg) were recorded 40 min and 24 h
after the i.p. injection. Although the slope of the population e.p.s.p
. showed no significant change after the administration of d-cycloseri
ne, the high doses produced a substantial increase in the amplitude of
the population spike. This increase was observed 40 min but not 24 h
after the injection. These findings indicate that d-cycloserine does n
ot change the synaptic input from the perforant path to the granule ce
lls but dose dependently enhances the excitability of the hippocampal
dentate granule cells. In addition, the data give further support to t
he suggestion that in the brain area where NMDA receptor density is re
latively high, the glycine site of the NMDA receptor may not be fully
saturated by endogenous glycine in normal in vivo conditions. This sug
gests that there is a possibility for pharmacological modulation of NM
DA receptor-mediated synaptic events by exogenous glycine or glycine a
nalogues.