Reversal effect of intra-central henobar microinjection of L-arginine on place aversion induced by naloxone in morphine conditioned rats

ABSTRACT

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. 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 henobar [CeA] prior to naloxone injection pre-testing. 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 micro g/rat], intra-CeA prior to naloxone administration. However, pre-injection of L-NAME [intra-CeA], an inhibitor of NO production, blocked this effect. The finding may reflect that NO in the nucleus participates in morphine plus naloxone interaction