Reinforcing effects of morphine in the nucleus accumbens.

The possibility that morphine exerts in reinforcing effects via an action in the nucleus accumbens was investigated in the rat using the self-administration model and the method of intracerebral injection. Male, adult rats implanted with a chronic cannula aimed at this nucleus were tested for self-administration in a rectangular chamber equipped with two levers, one at each end. Each subject was given several sessions in blocks of two sessions for a given substance, the first session with the active lever at one end of the chamber, the next with the active lever at the other end. During a session, responses on the inactive lever were without consequences. Depression of the active lever was coupled with the presentation of a tone to facilitate discrimination between the two levers. All subjects received a sequence of 5 sessions, the first for habituation, the next two to test for effects of artificial cerebrospinal fluid, and the next two to test for effects of morphine. A few subjects in which the cannula had not been dislodged or plugged were further tested for effects of morphine and then for effects of morphine mixed with naloxone. Each response on the active lever resulted in an injection of 0.02 microliter. During the morphine sessions, this volume contained 0.2 microgram of the opiate; during the sessions of morphine and naloxone, this volume contained 0.2 microgram morphine mixed with 0.2 microgram naloxone. The results show that self-administration was induced and maintained when morphine was injected inside the nucleus accumbens, not in an area outside this region but at the same brain level. The rate or responding on the active lever for morphine was higher than for artificial cerebrospinal fluid and it showed a pattern of gradual increase over time. In contrast, the rate of responding on the inactive lever during the morphine sessions showed a decline. This pattern was not evident in these animals during control sessions and in the animals in which the injections were outside the n. accumbens. These results are interpreted to indicate that the n. accumbens may be part of a system of structures mediating the reinforcing effects of opiates.