Dynorphin A-(1-13) attenuates withdrawal in morphine-dependent rats: effect of route of administration

Rats were made tolerant to morphine by subcutaneous implantation of morphine alkaloid pellets. Three days after pellet implantation, withdrawal was induced by pellet removal and was assessed 6 h later. Immediately prior to withdrawal assessment, rats were injected with dynorphin A-(1-13) either i.th. (via a catheter), i.c.v. (via a cannula) or i.v. (via the tail vein). When administered i.th. in the dose range 1.25-5 nmol/rat, dynorphin A-(1-13) attenuated withdrawal over the 40 min observation period. Similarly, dynorphin A-(1-13) administered i.v. (37.5-150 nmol/kg) attenuated withdrawal, though only over the first 20 min following administration. Dynorphin A-(1-13) up to 10 nmol/rat had no effect on withdrawal scores. These data indicate that dynorphin acts at spinal sites to suppress withdrawal in morphine-dependent rats and may play a role in tolerance and dependence mechanisms.