Kindling-induced changes in morphine analgesia and catalepsy: evidence for independent opioid systems

Repeated stimulation of the amygdaloid complex in rats results in the kindling of epileptic seizures. During the process of kindling and prior to the appearance of full behavioral convulsions, naloxone-sensitive changes in responsiveness to noxious stimulation occur, which disappear with repeated stimulation. When full behavioral convulsions appear, a short period of post-ictal behavioral depression (PID) can be seen immediately following convulsions. Naloxone either attenuates or completely blocks the occurrence of the PID. In order to test further the opioid nature of these phenomena, the development of tolerance to PD with repeated stimulation and the development of cross-tolerance to the analgesic and motor depressant effects of morphine were tested in kindled animals. Repeated elicitation of full behavioral convulsions resulted in a progressive decrease of PID duration across days. PID was also decreased in morphine tolerant animals. Repeated convulsions also induced cross-tolerance with both morphine analgesia and morphine-induced catalepsy. In contrast, animals tested following 10 days of amygdaloid stimulation which did not cause full behavioral convulsions to develop, showed cross-tolerance to the analgesic but not the motor depressant effect of morphine. The possibility that two different opioid systems, which are independent of one another are activated during different phases of kindling is discussed.