Effects of a novel potential antidepressant on the behavior and cortisol levels of isolated guinea pig pups

A novel, potential antidepressant, E-6006 citrate (E-6039), dose-dependentl y reduced the vocalizations emitted by isolated guinea pig pups. The (+)-E- 6006, but not the ( -)-E-6006, enantiomer also reduced vocalizing. There we re no reliable effects of E-6039 on locomotor activity, crouching, or other behavioral measures, but both E-6039 and the (+)-E-6006 enantiomer elevate d plasma cortisol levels during isolation. The contrasting effects of E-603 9 on vocalizations and plasma cortisol are discussed in terms of E-6039's p utative ability to inhibit release of substance P. The reduction in the voc alizations of isolated guinea pig pups corroborates positive results with t his drag in other antidepressant screens utilizing mice and rats, and provi des further support for the potential of E-6039 as an antidepressant compou nd. (C) 2001 Elsevier Science Inc. All rights reserved.