Pro-cognitive effect of acute imipramine administration correlates with direct interaction of BDNF with its receptor, Trkβ.

Given the important role of brain-derived neurotrophic factor (BDNF)-mediated Trkβ signalling in the mechanism of action of antidepressants (ADs), we examined ligand-receptor interactions in the rat cingulate cortex using a proximity ligation assay (PLA) in response to acute and repeated administration of imipramine (IMI), followed by various drug-free periods. Both the acute and chronic administration of IMI increased the BDNF-Trkβ interaction observed 3 h after drug administration. Withdrawal of IMI for 72 h or 7 days did not alter BDNF-Trkβ interaction. A significant reduction in this interaction after chronic IMI administration followed by 21 drug-free days was observed, but it returned to the control value when a new dose of IMI was given after this time. The level of mRNA encoding BDNF or Trkβ did not change in the experimental groups of animals, so one can conclude that alterations in the BDNF-Trkβ interaction depend not on acute vs. repeated treatment with IMI but on the presence of the drug in the body. This effect correlates well with the strong pro-cognitive effect of acute IMI, assessed by the novel object recognition (NOR) test.

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