NMDA-evoked currents in motor neurons of spinal cord slices from rats 7-10 days old display ethanol (EtOH) withdrawal hyperresponsiveness, as a rebound of currents to levels above control after exposure to 100 mM EtOH and wash. The non-specific PKC inhibitor H7 decreased the occurrence of withdrawal (Li & Kendig, SFN 2001). In the present report, we carried out electrophysiological and immunocytochemical experiments to test the hypothesis that the PKCγ isoform mediates the EtOH withdrawal. Excitatory postsynaptic currents were evoked by picosprizing 2 mM NMDA onto single motor neurons using patch clamp techniques in slices taken from p7-10 rat spinal cord lumbar section. EtOH (100 mM, 20 min) depressed the area of currents to 70 ± 4% (n=11) of control. On washout, current area rebounded to 132 ± 6% (n=11) of control. A PKCγ isoform-specific peptide inhibitor, applied 30 min before EtOH, concentration dependently suppressed the withdrawal. Immunocytochemical analysis revealed that spinal cord motor neurons ...