Effects of acutely and chronically administered antidepressants on the brain regional 3-methoxy-4-hydroxyphenylethyleneglycol sulfate in the forced swimming rat

The reducing effect of desipramine (DMI) on the duration of immobility induced in rats by forced swimming was markedly potentiated after chronic injection of the lower dose, whereas the action of chronic amitriptyline (AMI) was similar to that of acute treatment. MHPG-SO₄ in most of the brain regions, particularly that in the septal area, was increased by the forced swimming. Unlike the effect in the normal rats, acutely administered AMI and DMI did not reduce MHPG-SO₄ in the brain regions other than the septal area in the forced swimming rats. Similar to the effect in the normal rats, chronic treatment with DMI increased MHPG-SO₄ in the cortex, hippocampus and the thalamus in the forced swimming rats. In these rats, MHPG-SO₄ in the septal area was still lowered by both drugs. These results indicate that 1) inhibitory effect of acutely administered AMI and DMI on the presynaptic noradrenergic neurons disappears in most of the brain regions after the forced swimming, 2) chronic treatment with DMI increases the noradrenergic activity in the cortex, hippocampus and thalamus and 3) both acute and chronic treatments with the drugs inhibit the forced swimming-induced increase in noradrenergic activity in the septal area. The relevance of these effects to the behavioral action of the drugs is discussed.