Prefrontocortical dopamine depletion induces antidepressant-like effects in rats and alters the profile of desipramine during Porsolt's test.

The objective of this study was to investigate whether bilateral dopamine depletion within the medial prefrontal cortex affects depression state, as well as the antidepressant efficacy of desipramine, in the forced swimming test. The rat's behaviour was evaluated by quantifying duration of immobility, climbing, swimming and diving. Immobility latency was also quantified and proved to be a suitable novel parameter. Monoamine levels within the medial prefrontal cortex were measured by high-performance liquid chromatography during Porsolt's test, as well as one week after it. While Porsolt's test was followed by a typical depression-like profile in sham rats, depletion of prefrontocortical dopamine (86% vs sham controls) reduced immobility and enhanced swimming, which is consistent with a diminished depression tonus. The observed enhancement of swimming was correlated with a high prefrontocortical serotonergic neurotransmission. On the other hand, desipramine induced antidepression-like effects in sham rats by increasing prefrontocortical noradrenaline and serotonin neurotransmisson, but also by blocking the normal increase in dopamine activity during the swimming test. Interestingly, desipramine behaved in a quite different manner in lesioned rats. Thus, immobility duration was not further reduced and only climbing, but not swimming, was enhanced. These effects were correlated with a preferential enhancement of noradrenaline neurotransmission. In conclusion, the results indicate that: (i) dopamine neurotransmission within the medial prefrontal cortex is a factor involved in depression, since dopamine reduction led to a low depression tonus; (ii) desipramine induces antidepression not only by enhancing prefrontocortical noradrenaline and serotonin neurotransmission, but also by blocking the normal increase in dopamine neurotransmission during a depressant situation; (iii) a selective enhancement of prefrontocortical serotonin neurotransmission mediates swimming; and (iv) a selectively augmented prefrontocortical noradrenaline activity mediates climbing during Porsolt's test.