A role for the parafascicular thalamic nucleus in the development of morphine dependence and withdrawal

The parafascicular thalamic nucleus (nPf) is a critical relay in the ascending system that mediates motor control in the central nervous system (CNS). Yet, little is known about whether or not the nPf is involved in the development of morphine dependence and withdrawal. In the present study, kainic acid was used to chemically destroy the nPf in Wistar rats, and morphine dependence and withdrawal models were established. Morphine withdrawal symptoms score was evaluated in each group, An electrophysiological method was used to measure the changes in spontaneous discharge of nPf neurons. mu-Opioid receptor (MOR) mRNA level in nPf was detected using semi-quantitative RT-PCR. The ultrastructural alterations were examined by transmission electron microscopy. Results showed that the bilateral lesion of nPf had a marked influence on the development of morphine dependence and withdrawal. In order to address the mechanisms underlying, we found: (1) the average frequency and sum of nPf neurons that exhibited spontaneous discharge were increased in the morphine withdrawal group in comparison with the sham model group (P < 0.05); (2) MOR mRNA level in the nPf of the morphine dependence group was decreased in comparison with that of the sham model group (1.45 +/- 0.38 vs. 5.37 +/- 0.94, P < 0.01). In the morphine withdrawal group, which under-went 40 h withdrawal, the MOR mRNA level was higher than that in the morphine dependence group (2.97 +/- 0.73 vs. 1.45 +/- 0.38, P < 0.05) but still lower than that in the sham model group (P < 0.05); (3) the ultrastructural injuries of nPf neurons, which were in the nucleus, organelles and neuropil, were marked in the morphine dependent and withdrawal groups. our study indicated that nPf played an important role in the development of morphine dependence and withdrawal. The results suggest that nPf may become a therapeutic target for treating morphine withdrawal syndrome. (C) 2009 Elsevier B.V. All rights reserved.