DESENSITIZATION OF THE D-1 DOPAMINE-RECEPTORS IN RATS REPRODUCES A MODEL OF ESCAPE DEFICIT REVERTED BY IMIPRAMINE, FLUOXETINE AND CLOMIPRAMINE

1. The present study investigated the effect of long-term D-1 dopamine receptor stimulation on an animal model of depression derived from th e learned helplessness paradigm. 2. The model used is based on the esc ape deficit produced by a series of unavoidable shocks administered to rats 24 h before the test session. SKF 38393 administered acutely, co mpletely prevented the development of animal hyporeactivity, while giv en repeatedly produced tolerance to its own protective effect. Moreove r it also reduced the spontaneous escape reactivity of rats not expose d to the inescapable shocks. Animals chronically receiving SKF 38393 a nd showing a clearcut escape deficit, were treated daily with either i mipramine, fluoxetine, or clomipramine. After 21 days of combined trea tment the 3 antidepressants appeared equally effective in reverting th e behavioral deficit. Moreover, long term administration of both imipr amine or SKF 38393 down regulated D-1 dopamine receptor number in the prefrontal cortex, while the association of the two drugs resulted in a receptor density similar to that of control rats. 3. The present res ults further support the crucial role played by D-1 dopamine receptors in the control of animal reactivity to stressful stimuli and in the m echanism of action of imipramine. Moreover they show that the D-1 dopa mine receptor related escape deficit is sensitive also to compounds se lectively acting through the serotonergic neuronal system.