Self-inhibiting action of nortriptyline's anti-immobility effect at high plasma and brain levels in mice

Abstract

Animals were treated acutely with 0, 2.5, 5, 10, 20 and 40 mg/kg nortriptyline (NT) 30 rain before the tail suspension test (TST). They were sacrificed after test for evaluation of plasma and brain levels of NT. The antiimmobility effect increased with increasing doses and concentrations of the drug, reaching statistical significance (P<0.01, Dunnett test) at a dose of 20 mg/kg, 865 ng/ml in plasma and I1 gg/g in brain tissue. The anti-immobility effect was, however, blocked with the highest, non-toxic, concentrations. Results seem to indicate a biphasic curvilinear relationship between plasma and brain levels of NT and behaviour in mice.