Acute effects of direct dopamine agonists in the mouse behavioral despair test

All the dopamine agonists (apomorphine, dipropylamino-5,6-dihydroxytetrahydronaphtalene, piribedil, bromocriptine, CBM 36-733) tested in the 'behavioral despair' test performed in mice had a dose-dependent anti-immobility effect, with the exception of the D-1 dopamine agonist, SKF 38393. This effect occurred at doses that reduced locomotor activity and decreased colonic temperature. A profound hypothermia of the same amplitude resulted from the immersion in water of the control and apomorphine (Apo)-treated mice. The anti-immobility effect of dopamine agonists depends on the stimulation of central dopamine receptors; this effect was antagonized more easily by haloperidol than by domperidone, and dipropylamino-5,6-dihydroxytetrahydronaphtalene was more effective than amino-5,6-dihydroxytetrahydronaphtalene. Their high sensitivity to sulpiride make it likely that the receptors involved correspond to the D-4 subtype. Blockade of dopamine receptors by haloperidol for about 5 days induced a slight hypersensitivity to the Apo effects. In contrast, tolerance to Apo occurred after administration of Apo, 5 mg/kg s.c., 24 and 16 h before testing. These data might reflect the potential antidepressant activity of direct dopamine agonists.