Long-term opiate exposure leads to increase in synapsin I in rat spinal cord-dorsal root ganglion cocultures.

Cocultures of spinal cord and dorsal root ganglion cells contain relatively high concentrations of kappa-opiate receptors. We have previously shown that acute kappa-opiate agonist treatment reduces phosphorylation of synapsin I stimulated by depolarizing agents (such as 60 mM KCl). Here we show that prolonged opiate treatment increases the levels of synapsin I immunoreactivity in the cells. Several opiate agonists, such as U50488, ethylketocyclazocine, dynorphin, and [D-Ala2,D-Leu5]enkephalin, caused a 3.0-3.4-fold increase in the immunoreactive level of synapsin I. The effect of the kappa-agonist U50488 on the up-regulation of synapsin I was dose dependent and was blocked by the kappa-opiate antagonist norbinaltor-phimine. The results suggest that continued activation of opiate receptors by chronic agonist treatment up-regulates the levels of synapsin I. This increase in synapsin I could contribute to the development of tolerance to opiates.