HYPOTHALAMIC SUBSTRATE FOR THE POSITIVE REINFORCING PROPERTIES OF MORPHINE IN THE RAT

The question of whether morphine has reinforcing effects when applied at brain-stimulation reinforcing sites of the hypothalamus in the rat was studied with the method of self-administration. Adult, male rats were implanted with a combination cannula/probe for tests of selfstimulation and selfadministration. The test chamber had a lever at each end; one delivered 0.02 μl of a solution when it was depressed, the other nothing. In the first experiment, the active lever remained on the same side for all tests. The subjects were low to moderate selfstimulators. Morphine was tested at two concentrations, 5 μg/μl and 10 μg/μl. The vehicle was artificial cerebrospinal fluid with a pH of 5.7. Results showed significantly higher rates of responding on the active lever for morphine at the 10 μg dose than for artificial cerebrospinal fluid, and higher rates on the active lever than on the inactive one for morphine at the 10 μg dose, as compared with rates for the 5 μg dose. In the second experiment, high selfstimulators learned successfully to reverse repeatedly when the active lever delivering morphine (10 μg/μl) was changed from one side of the test chamber to the other in successive sessions. Results with a mixture of naloxone and morphine or with naloxone given intraperitoneally and morphine intrahypothalamically produced partial or total blockade of lever-pressing. These results are indicative of a specific action of morphine at sites that support selfstimulation behavior, and of these hypothalamic sites as neural substrate for the reinforcing effect of morphine. © 1979.