INCREASED EXPRESSION OF SYNAPSIN-I MESSENGER-RNA IN DEFINED AREAS OF THE RAT CENTRAL-NERVOUS-SYSTEM FOLLOWING CHRONIC MORPHINE TREATMENT

Chronic opiate administration leads to a selective regulation of sever al cellular proteins and mRNAs. This phenomenon has been viewed as a c ompensatory mechanism to the opiate signaling leading to the developme nt of opiate addiction. In this study, in situ hybridization histochem istry experiments were employed to investigate the effect of chronic m orphine treatment on synapsin I gene expression. We show here for the first time that prolonged morphine exposure causes a selective increas e in the mRNA levels of synapsin I in several brain regions which are considered to be important for opiate action. Quantitative analysis of the signals, obtained by hybridization of digoxigenin-labeled antisen se RNA probe, revealed a 5.8- and 7-fold increase of synapsin I mRNA l evels in the locus coeruleus and the amygdala of morphine-treated rats , respectively, as compared with control untreated rats. Increased exp ression of synapsin I mRNA was also observed in the spinal cord of mor phine-treated rats (by 3.8-fold). Since opiates were shown to attenuat e neurotransmitter release and reduce synapsin I phosphorylation, it i s suggested that the increase in synapsin I levels would lead to the r equirement of higher amounts of opiate agonists to obtain the opiate p hysiological effects. These results suggest that the increases in mRNA levels of synapsin I in these specific areas can be part of the molec ular mechanism(s) underlying opiate tolerance and withdrawal.