Differential involvement of the lateral and medial divisions of the septalarea on spatial learning processes as revealed by intracranial self-administration of morphine in mice

The present study was conducted to investigate the effects of morphine self -administration into either the medial or lateral divisions of the septal r egion on spatial discrimination abilities in mice. To this end, BALB/c mice received a dose of 5 ng/50 nl of morphine sulfate, via a stainless steel i njection cannula, inserted into either the medial septal area (MS) or the l ateral septal nucleus (LS), when they are close to the end of one of the tw o choice arms of a Y-maze (acquisition period). In these conditions a discr imination between the reinforced arm and the neutral arm is acquired in MS as well as in LS mice. However both acquisition and subsequent extinction ( vehicle only available) was more rapid in the LS group than in the MS group . Moreover, during the extinction period, numerous escape attempts from the Y-maze were observed for MS mice. When the dose of morphine was raised to 50 ng the pattern of acquisition was unchanged in the LS group. In contrast animals of the MS group learned to avoid the arm where the higher dose of morphine was delivered thus allowing us to conclude that in MS animals the drug effect became aversive at this higher dose. This possibility was direc tly investigated in a second experiment by closing the access to the neutra l arm. Thus, for a 5-ng dose the rewarding effect of morphine was demonstra ted in both MS and LS groups by the decrease of self-administration latenci es which, furthermore, were notably lower than in the discrimination situat ion. Moreover, with the dose of 50 ng of morphine the latencies were identi cal for the two groups and at their lowest value thus indicating that morph ine had similar appetitive effects in MS as well as in LS mice in this situ ation. Thus, the previously observed deficit of MS subjects, including esca pe attempts. disappeared when the dose of morphine was raised and the exper imental context simplified. These results which demonstrate differential fu nctional properties of these two septal divisions an discussed in terms of conflict resulting from the strongly appetitive effects of the morphine whi ch induces, in parallel, deleterious consequences on cognitive processing i n MS self-injected mice. (C) 1998 Elsevier Science B.V. All rights reserved .