Abstract

The aim of this investigation was to determine the brain regions which were most sensitive to the inhibitory effects of morphine on the shaking response of pentobarbital-anesthetized rats to ice water. The median inhibitory dose (ID50) of morphine sulfate administered intraventricularly was found to be 0.35 mug/rat. When morphine was bilaterally injected into different regions of the brain, the ID50 values ranged from 0.04 to 17.9 mug/rat. The lowest ID50 values (0.04-0.20 mug) were found in the periaqueductal gray, the medial preoptic area and the locus ceruleus. The ID50 values ranged from 0.65 to 1.6 mug for areas around the nucleus accumbens, the fasciculus retroflexus, the medical thalamus and the septal area; from 5.6 to 7.3 mug for various hypothalamic nuclei; and from 11.0 to 17.9 mug for the basal ganglia, reticular formation substantia nigra and the reticular nucleus of the thalamus. The brain areas with the lowest ID50 values are known to have thermoregulatory functions. The similarity of the shaking response to shivering is discussed. It is concluded that the central inhibitory effects of morphine on shaking are subserved by discrete neuroanatomical substrates located in medial subcortical structures.