Reversal Effect of Intra-Central Amygdala Microinjection of L-Arginine on Place Aversion Induced by Naloxone in Morphine Conditioned Rats

Background: Role of nitric oxide (NO) on expression of morphine conditioning using a solely classic task has been proposed previously. In this work, the involvement of NO on the expression of opioid-induced conditioning in the task paired with an injection of naloxone was investigated. Methods: Conditioning was established in adult male Wistar rats (weighing 200-250 g) using an unbiased procedure. Naloxone (0.05-0.4 mg/kg, i.p.), a selective antagonist of mu-opioid receptor, was administered once prior to morphine response testing. NO agents were administered directly into the central amygdala (CeA) prior to naloxone injection pre-testing. Results: Morphine (2.5-10 mg/kg, s.c.) produced a significant dose-dependent place preference in experimental animals. When naloxone (0.05-0.4 mg/kg, i.p.) was injected before testing of morphine (5 mg/kg, s.c.) response, the antagonist induced a significant aversion. This response was reversed due to injection of L-arginine (0.3-3 µg/rat), intra-CeA prior to naloxone administration. However, pre-injection of L-NAME (intra-CeA), an inhibitor of NO production, blocked this effect. Conclusion: The finding may reflect that NO in the nucleus participates in morphine plus naloxone interaction.