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Desipramine treatment reduces the long-term behavioural and neurochemical sequelae of early-life maternal separation

Glenda M. MacQueen , Karuna Ramakrishnan , Ravena Ratnasingan , Biao Chen , L. Trevor Young
DOI: http://dx.doi.org/10.1017/S1461145703003729 391-396 First published online: 1 December 2003

Abstract

Primate and rodent models of maternal separation have shown that repeated postnatal separation of young from the mother results in long-term changes to neurohormonal systems relevant to depression. To date, however, it remains unclear whether rodents that experience postnatal maternal separation display specific behavioural or biochemical features of depression in adulthood and whether these changes can be prevented by treatment with antidepressant drugs. We report here that maternally separated mice showed significantly shorter swim times on the forced swim test and significantly lower levels of brain-derived neurotrophic factor in dentate gyrus and CA3 regions of the hippocampus compared to control mice when assessed in adulthood. Neither of these differences was apparent in maternally separated mice that received chronic treatment with the antidepressant desipramine after maternal separation. These results suggest that intervention following early stress may eliminate the long-term vulnerability to behavioural and biochemical dysfunction that occurs following this early chronic stress.

Key words
  • Depression
  • forced swim test
  • maternal separation
  • neurotrophins
  • stress