Striatal neurochemistry of dynorphin-(1-13): in vivo electrochemical semidifferential analyses.

The striatal neurochemistry of dynorphin-(1-13) was studied by simultaneously measuring extracellular dopamine and serotonin voltammetrically and in vivo after the injection of dynorphin-(1-13) to male Sprague-Dawley rats. The subcutaneous administration of dynorphin-(1-13), at a dose (1.5 mg/kg), known to exert CNS mediated behavioral effects, caused a statistically significant decrease in extracellular dopamine and a statistically significant increase in extracellular serotonin from rat anterior striatum. These parallel and opposite effects of dynorphin-(1-13) on these biogenic amines occurred gradually during a three hour time course. Maximal effects on dopamine (55%) and on serotonin (62%) occurred at the end of the three hour period of study. Mean effects on dopamine and serotonin (35% and 42% respectively) were averaged from scan results over the three hour period of study; the results were significantly different from control values. Dose response studies showed that a lower dose of dynorphin-(1-13) (0.5 mg/kg sc) had little or no effect on the alteration of these biogenic amines from striatum. The highest dose of dynorphin-(1-13) studied, (3.0 mg/kg sc), predictably and significantly altered extracellular biogenic amines. The dose response, however, was not incremental. The results are consistent with the role of dynorphin-(1-13) as a neuromodulatory peptide. The results further support the concept that the neuromodulatory role of dynorphin-(1-13) may take place through neurotransmitter regulation. The data suggest that the function of dynorphin-(1-13) may be a presynaptic modulation of neurotransmission in striatum.