SELECTIVE EFFECTS OF ALFENTANIL ON NOCICEPTIVE-RELATED NEUROTRANSMISSION IN NEONATAL RAT SPINAL-CORD

We have examined the effects of alfentanil on nociceptive-related neurotransmission in isolated neonatal rat spinal cord, with particular attention to acute tolerance. Electrical stimulation of a lumbar dorsal root was used to evoke the monosynaptic reflex (MSR), a slow ventral root potential (sVRP), and the dorsal root potential (DRP). Alfentanil (0.5 nmol litre(-)1 to 1 mu mol litre(-1)) depressed sVRP area by a maximum of 85%; EC(50) was approximately 2 nmol litre(-1). The effects of alfentanil were selective for very slow, metabotropically mediated sVRP components compared with faster NMDA receptor-mediated components. The MSR was unaffected. Alfentanil depressed DRP area by a maximum of 50% at 1 mu mol litre(-1). Naloxone antagonized all alfentanil effects. Morphine depressed sVRP area with an approximate EC(50) of 90 nmol litre(-1), giving an alfentanil:morphine potency ratio of 45:1. The effects of alfentanil on sVRP showed no biphasic time dependence up to 60 min. Naloxone administered after alfentanil produced a significant rebound in sVRP area to a level of 143 (SD 21.3)% above control. Thus, in this study there was no evidence for acute tolerance, as measured by a decrease in effectiveness over time, but there was evidence as measured by rebound following naloxone.