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Neuroscience. 1993 Dec;57(4):973-83.

The sensitivity of hippocampal long-term potentiation to nitric oxide synthase inhibitors is dependent upon the pattern of conditioning stimulation.

Author information

1
Central Nervous System Biophysics and Molecular Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 06492.

Abstract

Inhibition of nitric oxide synthase prior to conditioning has been previously found to reduce levels of hippocampal long-term potentiation. In the present experiments in the rat, the reduction of long-term potentiation by nitric oxide synthase inhibitors was highly conditioning-dependent. We have characterized the relative importance of the number of conditioning stimulus trains, pulse number, intensity, and pattern in the reduction of long-term potentiation by nitric oxide synthase inhibitors. Long-term potentiation was reduced relative to control values only when multiple conditioning stimulus trains were presented at maximal stimulus intensity; potentiation produced by an equivalent number and intensity of stimuli presented in a single conditioning train was not reduced by nitric oxide synthase inhibitors, and multiple-train-induced potentiation was sensitive to nitric oxide synthase inhibitors only when maximal stimulation intensity was employed. Another form of synaptic potentiation, primed-burst potentiation, was reduced by nitric oxide synthase inhibition, while homosynaptic and heterosynaptic depression were unaffected. Our results support the hypothesis that conditioning-dependent release of nitric oxide can contribute to long-term potentiation, but also show that its blockade by nitric oxide synthase inhibitors is dependent on the nature of the conditioning stimulus, and that long-term potentiation can be generated that is apparently resistant to the effects of these drugs.

PMID:
7508586
DOI:
10.1016/0306-4522(93)90042-e
[Indexed for MEDLINE]

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