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 k‐opiate receptors. We have previously shown that acute k‐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 k‐agonist U50488 on the up‐regulation of synapsin I was dose dependent and was blocked by the k‐opiate antagonist norbinaltorphimine. 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.