Self-administration of D-Ala2-Met-enkephalinamide at hypothalamic self-stimulation sites

The relationship between the action of enkephalin and the reinforcing action of electrical stimulation in the posterior lateral hypothalamus of the rat was studied with the self-administration approach. Adult male albino rats implanted with a combination cannula and stimulation electrode in hypothalamus were pretested for the reinforcing effects of electrical stimulation. Only subjects that self-stimulated at moderate to high rates were given self-administration tests. The chamber for the self-administration tests was fitted with one lever at each end of a rectangular plexiglass box. In a session, one lever was 'active', the other not. The active lever, if depressed, yielded 20 nl of CSF (artificial cerebrospinal fluid), or CSF in which one of the test substances was dissolved. Each subject was tested repeatedly for the reinforcing effects first of a control solution (CSF), then of D-Ala2-Met-enkephalin (DALA), a long-acting synthetic analogue of enkephalin, then of morphine, and then of opioids mixed with naltrexone or naloxone. Following these tests, the subjects were once again given self-stimulation tests to ascertain the functional integrity of the 'reward' system after the repeated self-administration tests. The results demonstrate that when the test solution was DALA instead of CSF the subjects pressed the active lever at a higher rate than for CSF, and they exhausted the supply more rapidly than for CSF. The rate on the active lever was also significantly higher than on the inactive lever. DALA at 1 and 5 microgram/microliter concentrations proved more reinforcing than at 0.1 microgram/microliter. Naltrexone did not block the reinforcing effect of DALA, whereas naloxone blocked DALA-induced reinforcement. These data extend the report of ventricular methionine-enkephalin positive reinforcement to DALA injected directly into the lateral hypothalamus.