INFLUENCE OF NITRIC-OXIDE SYNTHASE INHIBITION ON THE DEVELOPMENT OF RAPID TOLERANCE TO ETHANOL

We recently reported that the nitric oxide (NO) synthase inhibitor L-n itroarginine (L-NA) blocks the development of rapid tolerance to the m otor incoordinating effect of ethanol in the tilt-plane test. To clari fy the mechanism of L-NA blockade of tolerance, four additional experi ments were carried out using the same test. The first demonstrated tha t L-NA prevented the development of rapid tolerance to ethanol when in jected prior to ethanol either on both Days 1 and 2 or only on Day 1. In the second experiment, tolerance was blocked only when L-NA was inj ected before but not after behavioral testing on Day 1. In the third, L-NA blocked the enhancement of rapid tolerance to ethanol induced by D-cycloserine (CS), an agonist at the N-methyl-D-aspartate (NMDA) rece ptor. In the last experiment, L-NA pretreatment did not influence bloo d ethanol disappearance curves on Day 1, or ethanol concentrations in brain, tail blood or decapitated trunk blood on Day 2. These data argu e against state-dependent learning as the basis of the L-NA effect, an d confirm and extend our previous observation that NO plays a role in the development of rapid tolerance to ethanol.