DYNORPHIN-A (1-13) POTENTIATES DYNORPHIN-A (1-17) ON LOSS OF THE TAIL-FLICK REFLEX AFTER INTRATHECAL INJECTION IN THE RAT

Dynorphin A (1-13) or dynorphin A (1-17) administered intrathecally to rats induces a dose-dependent loss of the tail-flick reflex and a reversible hindlimb paralysis. Although their potency is comparable, dynorphin A (1-17) is less efficacious in producing loss of the tail-flick reflex. These data suggest that dynorphin A (1-17) acts as a partial agonist or exerts its neurotoxic effect in the presence of an endogenous non-competitive inhibitor. To determine whether these substances act at similar sites we performed isobolographic analysis. This analysis revealed that dose-additivity exists for paralysis whereas deviation from dose-additivity exists for loss of the tail-flick reflex.