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Adenosine is a neuromodulator that has been proposed to be a major endogenous anticonvulsant acting via A₁ receptors. We tested if implementation of kindling through stimulation of the amygdala affected A₁ receptor‐mediated neuromodulation in hippocampal slices taken from rats 4 weeks after the last stage 5 seizure. The A₁ receptor agonist, N⁶‐cyclopentyladenosine (CPA) (6–100 nm), inhibited field excitatory postsynaptic potential (fEPSP) slope with an EC₅₀ of 19.1–19.5 nm in control and sham‐operated rats, but was less potent in kindled rats (EC₅₀ = 42.7 nm). This might result from a decreased number of A₁ receptors in hippocampal nerve terminal membranes, because A₁ receptor immunoreactivity decreased by 28 ± 3% and the binding density of the A₁ receptor agonist [³H]R‐PIA decreased from 1702 ± 64 to 962 ± 78 fmol/mg protein in kindled compared with control rats. The tonic …