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Journal of Neuroscience, Vol 14, 7415-7425, Copyright © 1994 by Society for Neuroscience
Inhibition of nitric oxide synthase does not prevent the induction of long-term potentiation in vivo
DM Bannerman, PF Chapman, PA Kelly, SP Butcher and RG Morris
Department of Pharmacology, University of Edinburgh Medical School, Scotland.
Nitric oxide (NO), a putative intercellular messenger in the CNS, may be
involved in certain forms of synaptic plasticity and learning. This article
reports a series of experiments investigating whether an inhibitor of NO
synthase, N omega-nitro-L-arginine methyl ester (L- NAME), affects
long-term potentiation (LTP) in vivo, as the results of recent in vitro
experiments would predict. L-NAME, given as an acute injection at a dose
sufficient to inhibit hippocampal NO synthase (> 90%), had no effect on
perforant path-dentate gyrus LTP induced by a strongly suprathreshold
tetanus, but appeared to impair LTP induced by a weak near-threshold
tetanus that may be more physiologically relevant. However, subsequent
studies revealed that chronic L-NAME treatment (> 95% inhibition of NO
synthase) had no effect upon LTP induction, and that acute (but not
chronic) treatment resulted in a gradual but significant reduction in
nontetanized baseline field potentials. The baseline shift appeared to be
of a magnitude sufficient to account for the apparent impairment of weak
tetanus-induced LTP. This possibility was further examined in a
two-hemisphere experiment in which the time course of changes in the field
EPSP of the nontetanized pathway served as the within-subject control for
the tetanized pathway. No impairment of LTP induction was observed; indeed,
if anything, there was a trend for greater potentiation with L-NAME.
Because NO has also been implicated in the control of vasodilation, the
effect of L-NAME on cerebrovascular function was also investigated.
Peripheral blood pressure was significantly increased by L-NAME at the same
dose that affected the field EPSP. Local cerebral glucose utilization was
unchanged, while local cerebral blood flow decreased significantly in
various brain regions, including the hippocampus, indicating an uncoupling
of cerebral metabolism and blood flow. Thus, while NO synthase inhibition
does not appear to limit the induction of LTP in vivo, it does reduce the
size of baseline field EPSPs and affect local cerebrovascular function.
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