A study of intrathecal self-injection of morphine by rats, and the difficulties entailed

Rats were chronically implanted with an intrathecal cannula, through which they were taught to self-administer morphine. After a training period of 2 weeks, their self-injection behaviour was studied before, during and after nociceptive stimulation. In response to nociceptive stimulation the rats increased their intrathecal self-injection of morphine. This effect is specific for morphine, since under the same conditions rats did not increase NaCl self-injection. Acute naloxone pre-treatment was shown to block the analgesic effect of intrathecal morphine administration. In the present experiments, morphine never induced convulsions or epilepsy. This suggests, first that the mode action of intrathecally injected morphine is located in the spinal cord and second, that the low dose (20-30 micrograms) of self-injected morphine is not sufficient to induce symptoms of convulsions or epilepsy. Our results show that the rats behave as if deliberately reducing the painful sensation. This experimental situation is therefore similar to the therapeutic situation in humans. It might, therefore, be used for preclinical evaluation of the efficacy of an analgesic drug.