Stereospecific blockade of marble-burying behaviour in mice by selective, non-peptidergic neurokinin1 (NK1) receptor antagonists

By analogy with the selective serotonin reuptake inhibitor, fluvoxamine, and the tricyclic agent, clomipramine, the novel, selective, non-peptidergic NK(1) receptor antagonist, GR205,171, dose-dependently and completely blocked marble-burying behaviour in mice: Inhibitory Dose(50)s (ID(50)s), 4.5, 4.8 and 7.6 mg/kg, respectively. In contrast to GR205,171, its isomer, GR226,206, which displays substantially lower affinity for NK(1) receptors, was inactive (> 40.0 mg/kg). By analogy with GR205,171, a further, selective NK(1) antagonist, RP67,580, abolished marble-burying behaviour with an ID(50) of 11.9 mg/kg. At doses significantly reducing marble-burying behaviour, GR205,171 and RP67,580 little influenced motor behaviour. In conclusion, like fluvoxamine and clomipramine, selective, non-peptidergic NK(1) receptor antagonists block marble-burying in mice. Although the biological bases of this behaviour remain unclear, these observations underpin the contention that NK(1) receptors may be implicated in affective disorders.