Biphasic effects of naloxone in the rats receiving morphine overdose a place preference study

Downward phase of dose-response morphine converted U shape curve was chosen as a base for investigating the effects of different doses of naloxone (0.05-0.4 mg/Kg) on morphine reward/aversion properties using place preference method. First, male Wistar rats (200-220 g) were received morphine (1-7.5 mg/Kg) for place conditioning and marginal dose of morphine (5 mg/Kg) calculated by GraphPad software. In the next part, the animals received different naloxone challenge doses (0.05-0.4 mg/Kg; IP) on the test day. Animals' behavior was monitored using a video camera during the test session. Time spent in each compartment was calculated as the main sign of drug seeking behavior. In addition, numbers of rearing and sniffing as well as locomotion activity for each animal were counted as important dopamine-dependent behavioral signs. More over, the total compartment crossing by each animal as the sign of decision making was also counted. Our results indicated that naloxone showed biphasic effects on the appearance of morphine-induced place preference. The antagonist potentiates the expression of morphine-induced place preference on the dose of 0.05 and 0.4 mg/Kg while inhibits the morphine effect on the dose of 0.1 mg/Kg. On the other hand, the total animal sniffing, rearing, locomotion, and compartment entering were not significantly changed among the groups. It could be concluded that the inhibition of opioid receptors may enhance or inhibit the expression of morphine reward according to the naloxone dose, which in turn indicate the influence of several opioid receptor in this regard. In addition, opioid receptor blocking did not enhance the signs of drug seeking behavior linked to the activity of mesolimbic dopamine system.