Blockade of the Naloxone-induced Aversion in Morphine-conditioned Wistar Rats by L-Arginine Intra-central Amygdala

Abstract

Objective(s) Single injection of naloxone, a selective antagonist of morphine, prior to the drug conditioning testing was used to investigate on morphine dependence. Materials and Methods Conditioning to morphine (2.5-10 mg/kg, s.c.) was established in adult male Wistar rats (weighing 200-250 g) using an unbiased procedure. Nitric oxide agents were microinjected into the central amygdala prior to naloxone-paired place conditioning testing. Results The results showed that morphine produced a significant dose-dependent place preference in animals. Naloxone (0.1-0.4 mg/kg, i.p.) injections pre-testing of the response to morphine (7.5 mg/kg, s.c.) caused a significant aversion at the higher doses (0.4 mg/kg, i.p.). This response was reversed by microinjection of L-arginine (0.3-3 µg/rat, intra-central amygdala) prior to naloxone on the day of the testing. The response to L-arginine was blocked by pre-injection of N G -nitro-L-arginine methyl ester (L-NAME) (intra-central amygdala). Conclusion A single injection of naloxone on the test day of morphine place conditioning may simply reveal the occurrence of morphine dependence in rats, and that the nitric oxide in the central amygdala most likely plays a key role in this phenomenon.