Sex differences in perforant path long-term potentiation (LTP) have been reported in pentobarbital-anesthetized rats. Because this effect may be due to the prominent sex difference in barbiturate sensitivity, the present report examined perforant path-dentate granule cell synaptic transmission and long-term potentiation (LTP) in adult male and female rats anesthetized with urethane. Spectral analysis of hippocampal electroencephalographic (EEG) activity indicated that urethane induced similar levels of anesthesia in male and female rats, and there were no sex differences in the latency or amplitude of extracellular field potentials evoked in the dentate gyrus following perforant path stimulation. In contrast, there was a robust sex difference in the magnitude of LTP induced in the dentate gyrus following high-frequency stimulation (HFS) of the perforant path. This sex difference in LTP was paralleled by a sex difference in the magnitude of N-methyl-D-aspartate (NMDA) receptor activation generated by perforant path HFS. These results demonstrate a sex difference in hippocampal LTP that cannot be explained by a sex difference in level of anesthesia.
