Repeated treatment with imipramine enhances the excitatory response of hippocampal neurons to dopamine.

The effect of imipramine on the responsiveness of CA1 pyramidal neurons to dopamine was studied in hippocampal slices, obtained from rats treated acutely or repeatedly with imipramine (10 mg/kg, 14 days, twice a day p.o.). In slices from non-treated rats the bath-applied dopamine evoked mainly potentiation, while SKF 38393 produced diminution of the firing rate of hippocampal CA1 neurons. Acute imipramine did not significantly affect the reactiveness of neurons to dopamine, whereas repeated imipramine administration increased both the strength and duration of the response to dopamine. In animals pretreated both acutely and repeatedly with imipramine, SKF 38393 induced the excitatory, and not the inhibitory response, the obtained effect being more potent after repeated administration of imipramine. Haloperidol antagonized the excitatory reaction to dopamine but not to SKF 38393. SCH 23390 did not affect the excitation evoked by dopamine and SKF 38393. It is concluded that repeated imipramine administration induces supersensitivity of hippocampal dopamine D2 receptors in the rat which--in the light of our earlier studies--are responsible for the dopamine-evoked excitatory effect in the rat hippocampal slices.