Antidepressant drugs attenuate 7-OH-DPAT-induced hypoactivity in rats

Various antidepressant drugs given repeatedly induce the supersensitivity of postsynaptic dopamine D2 and D3 receptors. Several reports have also suggested the subsensitivity of presynaptic dopamine D2 receptors. The aim of the present study was to investigate the effect of two antidepressant drugs with different pharmacological profile, i.e. imipramine and citalopram, administered repeatedly, on the hypoactivity induced by low dose (0.05 mg/kg sc) of (+/-)7-hydroxy-dipropylaminotetralin (7-OH-DPAT), a dopamine D3 receptor preferring agonist. Male Wistar rats were treated with antidepressant drugs (10 mg/kg po) either acutely (single dose) or repeatedly (twice daily for 14 days). Two or 24 h after the last dose of antidepressant drug, the locomotor activity induced by (+/-)7-OH-DPAT was measured in photoresistor actometers. Additionally, the influence of nafadotride (0.2 or 1 mg/kg ip), a dopamine D3 preferring antagonist, on the (+/-)7-OH-DPAT-induced changes in locomotor activity was studied. Low dose of (+/-)7-OH-DPAT induced the locomotor hypoactivity, however, this effect was not modulated by nafadotride. Antidepressant drugs given repeatedly, but not acutely, reversed the effect of (+/-)7-OH-DPAT, and this effect of antidepressants was antagonized by nafadotride. The obtained results indicate that the sensitivity of dopamine D3 receptors might be altered by the repeated treatment with antidepressant drugs.