Prolonged treatment with antidepressant drugs increases the excitatory effect of quinpirole in hippocampal slices.

The effects of single and repeated treatment with different antidepressant drugs, such as imipramine, mianserin and citalopram, on the responsiveness of the rat hippocampal neurons to the selective dopamine D-2 receptor agonist quinpirole were examined. The bath-applied quinpirole increased the firing rate of most of the studied CA1 layer neurons in a slice preparation. That excitatory response was attenuated by the selective D-2 receptor antagonist sulpiride. In hippocampal slices prepared from rats treated repeatedly with antidepressant drugs, the quinpirole-induced increase in the neuronal firing rate was significantly potentiated, compared to the quinpirole-induced effect in slices prepared from untreated animals. No change was observed in the reaction to quinpirole after a single dose of the antidepressant drugs used in the study. To determine whether the increase in the excitatory effect of quinpirole evoked by prolonged treatment with antidepressants is receptor-specific, or whether it reflects an unspecific increase in the neuronal responsiveness to excitatory agents, the effect of imipramine on the noradrenaline-induced excitation of CA1 neurons was studied. Prolonged, but not acute, treatment with imipramine decreased the beta-adrenergic receptor-mediated excitation evoked by noradrenaline. It is concluded that prolonged treatment with imipramine, mianserin and citalopram produces an increase in the responsiveness of hippocampal CA1 neurons to stimulation of the dopamine D-2 receptor.