Different strains of rats show different sensitivity to block of long-term potentiation by nitric oxide synthase inhibitors.

Nitric oxide is presumed to play important roles in the induction of synaptic plasticity and learning. Previous publications, however, reported contradictory results. Block of nitric oxide synthase (NOS) has been shown to impair the induction of long-term potentiation of synaptic transmission in some studies. Other studies observed a partial block of long-term potentiation depending on experimental conditions, while yet other studies did not find an effect of NOS inhibitors under any conditions tested. Some reasons for these differences had been identified, e.g. the temperature of the slice buffer, the age of the animals, and the specific stimulation protocols used. Still, even when taking these parameters into account, not all results can be explained. The present study compares three strains of rats and observes large differences in sensitivity to nitric oxide synthase (NOS) blockers on the induction of long-term potentiation. While Wistar rats showed an almost complete block of long-term potentiation when using the NOS inhibitors 7-nitro-indazole (30 mg/kg ip) or 1-(2-trifluoromethylphenyl) imidazole (TRIM; 150 nmol/5 microl icv), 117+/-5 S.E.M. of % of baseline slope values of excitatory postsynaptic potentials. Sprague-Dawley and Long-Evans rats showed no or only weak effects of drugs on the induction of long-term potentiation (166+/-17 S.E.M. of % of baseline slopes in Sprague-Dawley rats, 173+/-24 S.E.M. of % of baseline values in Long-Evans rats). The results could explain at least some of the discrepancies of the efficacy of NOS inhibitors on synaptic plasticity that is found in the literature. Such large strain differences suggest that results from studies that use laboratory rats could have strain-dependent components and should be generalised cautiously.