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 NK1 receptor antaaonist, 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 NK1 receptors, was inactive (> 40.0 mg/kg). By analogy with GR205,171, a further, selective NK, antagonist, RP67,580, abolished marble-burying behaviour with an ID50 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-poptidergic NK1 receptor antagonists block marble-burying in mice. Although the biological bases of this behaviour remain unclear, these observations underpin the contention that NK1 receptors may be implicated in affective disorders. (C) 2002 Elsevier Science Ltd. All rights reserved.