Reinforcing effects of brain microinjections of morphine revealed by conditioned place preference

Abstract

The previously documented place conditioning paradigm was used to study the reinforcing effects of cerebral microinjections of morphine. Rats with implanted cannulae experienced place conditioning procedures, involving morphine administration into the IV (0.5 or 10 microgram), III (10 microgram) or lateral (0.5-10 microgram) ventricles. Positive reinforcement, indicated by a significant preference for the place paired with morphine compared to the place similarly paired with control treatment, was seen in rats given 10 microgram morphine into the lateral ventricle. The rats given 10 microgram into the III ventricle also showed a preference, but the effect was not statistically significant. Positive reinforcement was subsequently demonstrated with morphine microinjections (10 microgram) into the lateral hypothalamus, periaqueductal gray or nucleus accumbens. No clear preferences were produced by morphine injections into the caudate-putamen, amygdala or nucleus ambiguus. Following the final place conditioning test, rats were re-administered the treatment dose and analgesia and body temperature were measured. All three sites associated with reinforcement evidenced hyperthermia, but only the periaqueductal gray evidenced a short-latency analgesia. Sites with null place conditioning were not associated with any major behavioral effects. Using (+) and (-)-morphine (10 microgram), it was demonstrated that only the active (-)-stereoisomer was effective in producing place preferences after injection into the periaqueductal gray. It was concluded that morphine administered directly into parts of the rat brain can produce place conditioning similar to that seen after systematically administered morphine. Morphine-produced place preference is not related to the acute depressant aspects of morphine, but may be related to the stimulant aspects.