1. ¹UMR 677 INSERM/UPMC, Institut National de la Santé et de la Recherche Médicale, Université Pierre et Marie Curie, NeuroPsychoPharmacologie, Boulevard de l'Hôpital, Paris Cedex, France
2. ²Centre National de la Recherche Scientifique, UMR 6036, Neuropsychopharmacologie Expérimentale, Institut Fédératif de Recherches Multidisciplinaires sur les Peptides 23, Unité de Formation et de Recherche Médecine et Pharmacie, Boulevard Gambetta, Rouen Cedex, France

Correspondence: Dr D Popa, UMR 677 INSERM/UPMC, Faculté de Médecine Pitié Salpêtrière, 91, Boulevard de l'Hôpital, 75634 Paris Cedex 13, France. Tel: +33 1 40 77 97 13; Fax: +33 1 40 77 97 90; E-mail: popa@ext.jussieu.fr

Received 19 April 2005; Revised 13 September 2005; Accepted 19 September 2005; Published online 9 November 2005.

Abstract

In depressed patients, sleep undergoes marked alterations, especially sleep onset insomnia, sleep fragmentation, and disturbances of the Rapid Eye Movement (REM) sleep. Abnormalities of rest-activity rhythms and of hypothalamic–pituitary–adrenocortical function have also been described in these patients. In the present study, we examined the presence of such abnormalities in a recently developed line of mice (Helpless mice-H) that exhibit depression-like behaviors in validated tests, compared to the nonhelpless (NH) line derived from the same colony. Experiments were essentially carried out in females for which previous studies showed marked differences between H and NH lines. Compared to NH mice, the H line exhibited (i) lower basal locomotor activity, (ii) sleep fragmentation, shift towards lighter sleep stages, and facilitation of REM sleep reflected by increased amounts and decreased latency, (iii) larger response to the REM sleep promoting effect of muscarinic receptor stimulation (by arecoline). In contrast, H and NH mice were equally responsive to the REM sleep inhibitory effect of 5-HT_1A receptor stimulation (by 8-OH-DPAT). In addition, a deficiency in delta power enhancement after sleep deprivation was observed in the H group, and acute immobilization stress in this group failed to elicit a REM sleep rebound and was associated with a long-lasting raise in serum corticosterone levels. These results further validate H mice as a depression model and suggest they might be of particular interest for investigating the neurobiological mechanisms and possibly genetic substrates underlying sleep alterations associated with depression.