Effects of tryptophan and serotonin uptake inhibitors on behavior in male transgenic transforming growth factor alpha mice.

Our findings have implicated that transgenic male mice overexpressing human growth factor alpha (TGF alpha) exhibit lengthened immobility in the swim test and elevated levels of aggression in the resident-intruder test. Further, these animals have a reduced ratio between the metabolite of serotonin (5-HT), and 5-HT in the brain. The present study investigated whether pharmacological manipulations of serotonergic transmission affect the altered behavioral patterns of the male TGF alpha mice. For that purpose, we used tryptophan (0, 50 or 100 mg/kg), a precursor substance to 5-HT, and 5-HT uptake inhibitors, zimelidine (0, 12.5 or 25 mg/kg) and clomipramine (0, 10 or 20 mg/kg). Administration of tryptophan or zimelidine significantly shortened immobility in the swim test in the TGF alpha male mice. Tryptophan or clomipramine did not influence the male non-transgenic CD-1 mice, and zimelidine significantly lengthened their immobility. High levels of aggression were completely reversed by zimelidine or clomipramine in the transgenic male mice. Neither of these compounds altered behavior of the control mice in the resident-intruder test. Tryptophan failed to affect aggressive behavior in the TGF alpha or control male mice. These results suggest that TGF alpha may influence behavior by affecting the uptake of 5-HT in neurons.