Prolonged analgesia induced by cathinone. The role of stress and opioid and nonopioid mechanisms

Cathinone, the active principle of Catha edulis (khat), shows long-lasting analgesic effects when the tail-flick test is used in rats. The involvement of monoamines, endogeneous opioids and stress in this analgesic effect was tested. Both early (30 min) and late (24 h) analgesic effects of cathinone were prevented by reserpine or p-chlorophenylalanine, which deplete catecholamines or serotonin, respectively, and by nomifensine, which prevents neuronal uptake or biogenic amines and amphetamines. The same inhibitory effect was obtained with a high dose (4 mg/kg) of naloxone. However, rats made tolerant to morphine retained both early and late analgesic response to cathinone. The increase in plasma ACTH induced by the tail-flick test at 30 min and 24 h was significantly enhanced by cathinone, in a naloxone-reversible way. However, the analgesic responses shown at these times were not prevented by either dexamethasone or adrenalectomy. We conclude that the prolonged analgesia induced by cathinone is primarily due to an amphetamine-like activation of monoaminergic pathways, but requires the integrity of non-μ-opioid mechanisms. The involvement of the adrenohyophyseal axis in this cathinone effect is less probable.