Differential modulation of withdrawal reflexes by a cannabinoid in the rabbit

Inhibition of spinal and trigeminal withdrawal reflexes by morphine and by the cannabinoid agonist HU 210 has been studied in anaesthetized and in decerebrated rabbits. In intact, pentobarbitone-anaesthetized animals, the jaw-depressor reflex (JDR) evoked by stimulation of the tongue, and the reflex elicited in the ankle flexor tibialis anterior (TA) by stimulation of the toes were inhibited to the same extent by morphine (1-30 mg kg(-1) i.v. cumulative). In spinalized, anaesthetized rabbits morphine depressed the JDR to the same level as in non-spinal preparations, but the effect of the opioid on the TA reflex was significantly reduced. All effects of morphine were reversed by naloxone (0.25 mg kg(-1), i.v.). In anaesthetised intact animals, HU 210 depressed the JDR at a dose of 100 nmol kg(-1) i.v. cumulative, reduced reflexes evoked in the knee flexor muscle semitendinosus (ST) by stimulation at the toes at a dose of 30 nmol kg(-1) i.v. cumulative, but had no consistent or significant effects on the TA reflex to toe stimulation. The same results were obtained in spinalized, anaesthetised animals. In decerebrated, spinalized rabbits with no anaesthesia, HU 210 (30 nmol kg(-1)) depressed both ST and TA reflexes evoked by toe stimulation. These data reveal that trigeminal and spinal withdrawal reflexes are equally sensitive to morphine provided the spinal cord is intact, suggesting that at least part of the action of systemic morphine is due to activation of descending inhibition. The present results also show for the first time that cannabinoid agonists can inhibit trigeminal withdrawal reflexes. HU 210 had differential effects on the three reflexes studied depending on the presence or absence of anaesthesia. This is the first occasion on which we have found pharmacological distinctions between withdrawal reflexes, and indicates that spinal sensorimotor processing is more heterogeneous than has been suspected previously.