Conditioned effects of heroin on the expression of inducible nitric oxide synthase in the rat are susceptible to extinction and latent inhibition

Rationale The administration of heroin has been shown to inhibit the induction of nitric oxide, a molecule known to play a critical role in immune function. Previous research has shown that this alteration can be conditioned to environmental stimuli that have been associated with drug administration. However, it remains unknown whether the conditioned effects of heroin on nitric oxide formation follow accepted principles of learning. Objective This study sought to determine whether manipulations that induce extinction and latent inhibition, two learning paradigms known to reduce the expression of conditioned responses, would alter heroin's conditioned effects on the expression of inducible nitric oxide synthase (iNOS). Materials and methods The conditioning procedure involved repeated pairing of heroin administration with placement into a standard conditioning chamber. Rats were repeatedly exposed to the chambers without heroin reinforcement to determine whether the conditioned response would extinguish. To induce latent inhibition, rats received repeated exposure to the chamber before the start of conditioning to inhibit the acquisition of the conditioned response. Ten days after the final conditioning session, all rats were injected with lipopolysaccharide (LPS) to induce iNOS expression. Spleen and liver tissue were removed to determine iNOS expression using reverse transcriptase polymerase chain reaction. Blood was collected to determine the concentration of nitrite/nitrate. Results The results showed that both extinction and latent inhibition reduced the conditioned effects of heroin on the production of nitric oxide. Conclusion This study provides the first evidence that the conditioned effects of heroin on nitric oxide production follow accepted principles of learning.