Morphine induced alterations of gamma-aminobutyric acid and taurine contents and L-glutamate decarboxylase activity in rat spinal cord and thalamus: possible correlates with analgesic action of morphine.

Acute administration of morphine induced significant increases of gamma-amino-butyric acid (GABA) content and L-glutamate decarboxylase (GAD) activity at the dorsal parts of the dorsal horn and surroundings of the central canal in the rat spinal cord, in which GABA inhibitory interneurons may play significant roles. In the thalamus, morphine also induced significant increases of GABA content and GAD activity in the vicinity of the ventrolateral part of the ventral nucleus (VM), entopeduncular nucleus (EP), nucleus reuniens thalami (RE), nucleus parafascicularis thalami (PF) and interpeduncular nucleus (IP), respectively. The most significant increase of GABA was observed in the VM and PF, which are known to receive neuronal inputs from secondary neurons involved in the perception of pain. In spite of well-known involvement of periaqueductal gray matter (PVG) in the occurrence of morphine analgesia, GABA content in this area did not change following acute administration of morphine. The above mentioned increases of GABA in the spinal cord and thalamus were antagonized by the pretreatment with levallorphan, a narcotic antagonist, and were not observed when an analgesic dose of sodium salicylate or pentazocine was administered. On the other hand, acute administration of morphine failed to alter the microdistribution of taurine (2-aminoethanesulfonic acid) in the rat spinal cord and thalamus, in which significant increases of GABA content were observed. Contrary to the results obtained in acutely morphine-treated rats, animals rendered dependent by the implantation of a morphine pellet showed significant increases of taurine content in the spinal cord, whereas no change in GABA contents was detected in both spinal cord and thalamus. The present results suggest that morphine analgesia may involve mechanisms intensifying the inputs of GABA inhibitory neurons at the levels of the spinal cord and thalamus, where the primary and secondary neurons involved in the perception of pain are terminated respectively. Possible involvement of alterations in spinal taurine contents in the occurrence of morphine dependence are also suggested.