ELECTROPHYSIOLOGICAL ACTIONS OF ALFENTANIL - INTRACELLULAR STUDIES INTHE RAT LOCUS-CERULEUS NEURONS

1 The electrophysiological effects of alfentanil on 156 neurones of th e rat locus coeruleus were investigated by use of intracellular record ings from the in vitro brain slice preparation. 2 Bath application of alfentanil (5-100 nM) reversibly decreased the firing rate of all neur ones tested in a dose-dependent manner, with an IC50 4.1 nM. 3 Based o n inhibition of the spontaneous firing rate, alfentanil was 22 times m ore potent than morphine. 4 At 100 nM, alfentanil produced a complete inhibition of firing of all neurones tested (n = 62); the inhibition w as accompanied by a membrane hyperpolarization 17.0+/-0.8 mV (range 6. 1-30.3 mV, n = 62) and a reduction in input resistance 26.4+/-1.7% (ra nge 6.5-53%, n = 51). 5 The effects of alfentanil were antagonized by naloxone, with a dissociation equilibrium constant of 2.7+/-0.4 nM (n = 6). 6 The reversal potential for the alfentanil-induced hyperpolariz ation was - 110+/-2 mV (n = 9), which is approximately the potassium e quilibrium potential. 7 The alfentanil-induced hyperpolarization was b locked by caesium chloride and barium chloride. 8 These results indica te that alfentanil binds to mu-opioid receptors on the cell membrane o f neurones of the locus coeruleus. This leads to opening of the inward -going rectification potassium channels, resulting in the observed hyp erpolarization of the membrane.