Figure 7.
CB1 activation prevents the action of ethanol. (a) WIN2 decreased the IPSP, and the subsequent addition of ethanol did not alter the GABA response. Recovery toward control level was obtained after washout of the drugs (31 min) in this neuron. RMP was −75 mV. (b) Average time course from seven experiments: WIN2 (2 μM; t=0) diminished mean IPSP amplitudes to 60% of control, and prevented the ethanol-induced augmentation of IPSPs. Ethanol (44 mM) was applied at t=25 min. (c) The prevention of ethanol effects by WIN2 occurred through CB1 activation. WIN2 decreased mean IPSP amplitudes to 57% of control and addition of SR1 reversed this effect to 84% of control. Further addition of ethanol in the continued presence of WIN2 and SR1 markedly increased mean IPSPs to 136% of pre-WIN2 level. (d) Left: ethanol had no effect on the paired-pulse ratio when WIN2 was present in the bath. Right: the effect of WIN2 on PPF was reversed by SR1. Subsequent addition of ethanol in the continued presence of WIN2 and SR1 now decreased PPF, indicating that CB1 ligands and ethanol act at a presynaptic site to alter GABA transmission.