AIM To characterize the role of neuronal nitric oxide synthase (
nNOS) in
morphine dependence process in rats. METHOD The specific
antisense oligodeoxynucleotide (A olig) targeting nNOS and endothelial NOS (
eNOS) were designed according to these gene structures, and nNOS, eNOS and inducible NOS (iNOS) mRNA levels were determined by using the reverse transcription polymerase chain reaction (RT PCR) method. RESULTS The intrathecal treatment with nNOS A olig (0 6 nmol per rat) at 24 h prior to naloxone challenge could block the morphine
withdrawal symptoms including wet dog shaking, irritating, salivation, diarrhea, chewing and weight loss. A olig for eNOS (0 6 nmol per rat, it) only prevented the diarrhea and weight loss. The total ratings of morphine withdrawal symptoms as well as diarrhea and weight loss were attenuated by intraventricular (icv) nNOS A olig, however, icv A olig targeting eNOS, sense or mismatch oligodeoxynucleotide (it or icv) for nNOS was inactive. The iNOS mRNA expression, which has been found to exist in spinal cord, were increased and de creased during morphine dependence and withdrawal respectively. Moreover, nNOS mRNA levels were down regulated by intrathecal nNOS A olig, meanwhile, the iNOS mRNA levels in spinal cord were increased. CONCLUSION The results suggest that nNOS in spinal cord plays an important role in the expression of morphine withdrawal symptoms, and regulate the iNOS expression in spinal cord during morphine dependence.