MORPHINE PHYSICAL-DEPENDENCE INTENSIFICATION BY HYPOGLYCEMIA - NMDA RECEPTOR INVOLVEMENT

The destruction of N-methyl-D-aspartate (NMDA) receptor-bearing neuron s by insulin-induced hypoglycemia has long been known to be due to exc essively released aspartate and glutamate. In this study, the effects of NMDA-bearing neuron destruction by insulin-induced hypoglycemia on the development of morphine (M) physical dependence, which was found r eleated to functional states of NMDA receptors, were investigated. NMD A receptor antagonists CGP 39551 and MK-801 were used to see whether t hey could change intensity of precipitated abstinence syndrome by prev enting destruction. Therefore, two groups of fasting rats injected IP with physiological saline, and another two groups given IP 10 mg/kg CG P 39551 and 0.5 mg/kg MK-801 received 15 IU/kg crystalline zinc insuli n IF. After 2 h, the rats were orally given 2 x 4 mi of 5% glucose sol ution. On the third day, two pellets containing 75 mg base M were SC i mplanted to all rats. On the sixth day, they were IP given 2 mg/kg nal oxone (NL). Then jumps, wet-dog shakes, and defecation were counted wh ile diarrhea and ptosis were rated for 15 min. The rats given insulin manifested significantly more intense NL-precipitated abstinence syndr ome than controls. The rats administered CGP 39551 showed a less inten se physical dependence than those injected with only insulin. But, the intensity was still significantly higher than controls. In the rats t hat received MK-801, the abstinence syndrome was more or less equal to that in controls. The results were considered as evidence for the blo ckade by M of NMDA receptors and the prevention by NMDA receptor antag onists of NMDA-bearing neurons from destruction of insulin-induced hyp oglycemia.