Effects of dynorphin_1-13 on opiate binding and dopamine and GABA uptake in stroked cat brain

We previously reported that the opioid peptide dynorphin_1-13 improves survival chances in stroked cats. Some evidence also suggests that changes in dopamine and γ-aminobutyric acid (GABA) uptake may be associated with stroke. In the present study, therefore, we determined binding of the opiate [³H]ethylketocyclazocine (EKC), as well as dopamine and GABA uptake in various brain regions of control, stroked and dynorphin_1-13-treated stroked cats. Cats were stroked by middle cerebral artery occlusion. In the EKC binding study, the K_d of the high-affinity site of the occluded cortex was significantly increased, relative to that of both the unoccluded side and control cortex. Dynorphin_1-13treatment reversed this effect, lowering the K_d to control level. In the dopamine uptake study, the K_m was decreased and V_max was increased significantly in unoccluded cortex, compared with that in the occluded cortex or in control cortex. Again, dynorphin_1-13 reversed these effects, raising the K_m and lowering the V_max. However, the K_m of occluded cortex was also increased so that it became significantly higher than that of control cortex. The K_m of unoccluded subcortex in stroked cats treated with dynorphin_1-13 was significantly reduced compared with control. In the GABA uptake study, there was no significant change in any parameter. The change in opioid binding observed here and its reversal by dynorphin_1-13 are consistent with the notion that the peptide's beneficial effect on stroke is mediated through opiate receptors. Since opioid systems in the brain are known to have association with dopaminergic ones, the change in dopamine uptake could also be the result of an opioid effect.