title: Reduction in preference for saccharin by repeated unpredictable stress in mice and its prevention by imipramine.
abstract: The present study set out to establish the chronic mild stress (CMS) animal model of depression in male CD-1 mice, a commonly used mouse strain. Mice were exposed to a series of mild stressors (e.g. soiled bedding, paired housing, cage tilt, white noise) presented in a continuous unpredictable fashion. Intermittently, CMS was discontinued and the mice were presented with both water and a palatable saccharin solution (0.1% w/v) in a two-bottle choice test overnight (15 h). Repeated exposure of these mice to the stressors led to a reduction in preference for the saccharin solution. This change in preference was attributed to an increase in the consumption of water rather than a decrease in the consumption of saccharin solution. Over time and with extensive testing, CMS no longer affected performance in the two-bottle saccharin preference test. Treatment with the tricyclic antidepressant imipramine (20 mg/kg i.p., once daily) had a varied effect on the CMS-induced change in preference for saccharin, dependent on the timing of initiation of imipramine treatment. In the first instance, following 5 weeks of CMS where a reduction in saccharin preference was established, treatment with imipramine for a further 5 weeks maintained the stress-induced deficit in saccharin preference. However, using a different approach, pre-treatment with imipramine once daily for 2 weeks, prior to onset of CMS, and co-treatment thereafter, attenuated CMS-induced changes in saccharin preference. Finally, when imipramine treatment was scheduled to begin with the CMS procedure, imipramine failed to prevent the CMS-induced reductions in saccharin preference. Changes in behaviour observed after exposure to CMS may be linked to a stress-induced deterioration of the sensitivity of the mice to a rewarding stimulus. Treatment with imipramine can reduce these behavioural changes but is only effective when given repeatedly prior to onset of CMS.
authors.affiliation: Department of Pharmacology, National University of Ireland, Galway. andrew.harkin@nuigalway.ie
authors.forename: Andrew
authors.initials: A
authors.lastname: Harkin
authors.forename: Diarmaid D
authors.initials: DD
authors.lastname: Houlihan
authors.forename: John P
authors.initials: JP
authors.lastname: Kelly
mesh_terms: D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001835:Body Weight / Q000502:physiology; D003259:Consummatory Behavior / Q000187:drug effects / Q000502:physiology*; D004326:Drinking / Q000187:drug effects / Q000502:physiology; D006120:Grooming / Q000187:drug effects; D006234:Handling, Psychological; D007099:Imipramine / Q000494:pharmacology*; D008027:Light / Q000009:adverse effects; D008297:Male; D051379:Mice; D009812:Odorants; D015203:Reproducibility of Results; D012439:Saccharin / Q000494:pharmacology; D012931:Social Environment; D013315:Stress, Psychological / Q000523:psychology*; D013649:Taste / Q000187:drug effects / Q000502:physiology*
chemical_list: D000929:Antidepressive Agents, Tricyclic; D012439:Saccharin; D007099:Imipramine