Preference for self-administration of a low dose of morphine into the ventral tegmental area rather than into the amygdala in mice

Abstract

BALB/c mice were bilaterally implanted with two guide cannulae, the tips of which were positioned either 1.5 mm above the amygdala (AMY) and the ventral tegmental area (VTA)(AMY-VTA subjects) or 1.5 mm above the AMY and 2.3 mm above the VTA (D.vta)(AMY-D.vta subjects). On each experimental day, a stainless steel injection cannula was inserted into each brain structure. The experiment was carried out in a Y-maze. During a preliminary phase, which lasted 4 days, animals were allowed to self-inject morphine successively into the AMY and into the VTA, or into the AMY and into the D.vta. From the 5th day, animals of each group were given the possibility of choosing between the two sites. Four subgroups were constituted depending on the dose of morphine used (5 and 50 ng: AMY5ng-VTA5ng, AMY50ng-VTA50ng, AMY5ng-D.vta5ng, and AMY5ng-D.vta50ng). The AMY5ng-VTA5ng group rapidly differentiated between the two injection sites and showed a marked preference for self-injection into the VTA. In the AMY50ng-VTA50ng group, no significant preference was observed, with the animals tending to alternate self-injection into the AMY and VTA. The AMY5ng-D.vta5ng group discriminated between the two sites and self-injected morphine preferentially into the AMY. The discrimination performance of the AMY5ng-D.vta50ng group was not statistically different from that at chance level. These results demonstrate that mice are capable of discriminating, at the intracerebral level, the motivational or rewarding components of morphine when the dose available is low (5 ng). The preference manifested is highly influenced by the location of injection cannulae. The positive effect of a low dose of morphine appeared stronger in the VTA than in the AMY. However, the location of injection cannulae 0.8 mm above the VTA induced a marked preference for self-injection into the AMY. Consequently, the rewarding effects of morphine into the VTA probably results from a local action of the drug and not from a dorsal diffusion.