These experiments investigated the action of histamine on local inhibition in the CA1 region of the in vitro hippocampal slice preparation using a paired-pulse paradigm. 2. We observed that histamine produced a concentration-dependent and reversible attenuation of paired-pulse inhibition. This effect was reduced by the H2 receptor antagonist, cimetidine, and mimicked by the H2 receptor agonist, impromidine. 3. We also observed that histamine produced concentration-dependent effects on the amplitude of the population spike that could be correlated with alterations in the field excitatory postsynaptic potential (EPSP) amplitude and input fiber volley. High concentrations of histamine produced a reduction in the amplitude of the population spike which was always accompanied by a reduction in the EPSP and fiber volley amplitude. 4. These results suggest that histamine, through the occupancy of H2 receptors, acts to modulate the efficacy of the local synaptic circuitry which is involved in producing paired-pulse inhibition in the hippocampus.
