The effect of acute and prolonged treatment with citalopram on the action of dopamine and SKF 38393 in rat hippocampal slices.

The effect of acute and prolonged treatment with the 'atypical' antidepressant, citalopram, on the responsiveness of CA1 layer neurons to dopamine and SKF 38393 was studied in a hippocampal slice preparation from rat brain. Dopamine applied to slices prepared from non-treated rat brain evoked either an increase or a decrease in the spontaneous neuronal firing rate, while a selective D-1 receptor agonist, SKF 38393, and a selective D-2 receptor agonist, LY 171555, respectively evoked mainly an inhibitory and excitatory reaction. Both acute and repeated citalopram administration (10 mg/kg twice daily p.o.) were found to change the inhibitory action of SKF 38393 into excitation and to potentiate the excitatory reaction to SKF 38393. The latter effect of citalopram increased with time after drug withdrawal. Acute citalopram administration potentiated the excitatory effect of dopamine while chronic treatment with the drug increased the proportion of units reacting with excitation and significantly decreased the number of units which showed an inhibitory reaction. It is concluded that citalopram affects the dopaminergic system in the hippocampus by diminishing the incidence of the inhibitory reaction to dopamine agonists, this effect being related to D-1 dopamine receptors, and by potentiating the excitatory reaction related with D-2 dopamine receptor activation.