Dose-discrimination performance of mice for self-administration of morphine into the lateral hypothalamus

Abstract

Two experiments were performed in BALB/ c mice implanted bilaterally with guide cannulae. In the first experiment, the tips of the guide cannulae were positioned 1.5 mm above the lateral hypothalamus (LH). On each experimental day, injection cannulae were inserted into each side of the LH. The experiment, carried out in a Y-maze, was composed of two phases. During the initial acquisition period, which lasted 4 days, animals were allowed to self-inject, successively, on alternate days, one dose of morphine into one side of the LH and a different dose in the other side. From the fifth day, the subjects were given the possibility of choosing between these two doses by entering into a given arm of the Y-maze. When the two doses available were 5 ng and 50 ng or 15 ng and 50 ng, the subjects rapidly discriminated them and preferentially triggered the injection of the higher dose (50 ng). When the two doses available were 30 ng and 50 ng, the mice triggered indifferently the two doses during the first three sessions. A discrimination between these two doses began to become apparent from the fourth session, with the subjects preferring to trigger the dose of 50 ng. In a second experiment, the tips of the guide cannulae were positioned either 1.5 mm or 2.6 mm above the LH, the bilateral injection cannulae consequently being inserted either into the LH or into the overlying ventral thalamus (TH). Experimental conditions were the same as that of Experiment 1. During a preliminary phase (4 days), animals were allowed to self-inject morphine successively into the LH or the TH, on alternate days. From the fifth day, subjects were given the possibility of choosing between the two sites. For one group, a single low dose of morphine (5 ng) was applied in both structures. In an other group, the doses used were, respectively, 5 ng for the LH and 50 ng for the TH. A marked preference for injection into the LH was observed in the two groups. These results show that mice are capable of discriminating, at the intracerebral level, the motivational or rewarding components of two different doses of morphine even when the dose levels are relatively close (30 ng vs. 50 ng). Moreover, these effects of morphine seem to remain localized to the proximity of the injection sites, suggesting strongly that opiate receptors present in the LH mediate the self-administration response for the drug in this brain region.