Aging impairs the antidepressant-like response to citalopram in male rats

Herrera-Pérez, José Jaime; Martı́nez-Mota, Lucı́a; Fernández‐Guasti, Alonso

doi:10.1016/j.ejphar.2010.01.022

Cited by 22 publications

(14 citation statements)

References 33 publications

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“…Yet, very late-onset depression in elderly humans (who have relatively low IGF-1 levels) can be resistant to antidepressants (Meyers & Jeste, 2010). Furthermore, older rodents show a decreased behavioral and neurogenic response to SSRIs (selective serotonin reuptake inhibitors) (Herrera-Perez et al, 2010), providing evidence that depression may be regulated through multiple pathways. Also, growth hormone is produced in the hippocampus (Donahue et al, 2006), and its pathways may interact and/or have IGF-1 independent effects on mood.…”

Section: Discussionmentioning

confidence: 99%

Long-term deficiency of circulating and hippocampal insulin-like growth factor I induces depressive behavior in adult mice: a potential model of geriatric depression

et al. 2011

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Numerous studies support the hypothesis that deficiency of insulin-like growth factor I (IGF-1) in adults contributes to depression, but direct evidence is limited. Many psychological and pro-cognitive effects have been attributed to IGF-1, but appropriate animal models of adult-onset IGF-1 deficiency are lacking. In this study, we use a viral-mediated Cre-loxP system to knockout the Igf1 gene in either the liver, neurons of the CA1 region of the hippocampus, or both. Knockout of liver Igf1 reduced serum IGF-1 levels by 40% and hippocampal IGF-1 levels by 26%. Knockout of Igf1 in CA1 reduced hippocampal IGF-1 levels by 13%. The most severe reduction in hippocampal IGF-1 occurred in the group with knockouts in both liver and CA1 (36% reduction), and was associated with a 3.5-fold increase in immobility in the forced swim test. Reduction of either circulating or hippocampal IGF-1 levels did not alter anxiety measured in an open field and elevated plus maze, nor locomotion in the open field. Furthermore, local compensation for deficiencies in circulating IGF-1 did not occur in the hippocampus, nor were serum levels of IGF-1 upregulated in response to the moderate decline of hippocampal IGF-1 caused by the knockouts in CA1. We conclude that adult-onset IGF-1 deficiency alone is sufficient to induce a depressive phenotype in mice. Furthermore, our results suggest that individuals with low brain levels of IGF-1 are at increased risk for depression and these behavioral effects are not ameliorated by increased local IGF-1 production or transport. Our study supports the hypothesis that the natural IGF-1 decline in aging humans may contribute to geriatric depression.

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Section: Discussionmentioning

confidence: 99%

Long-term deficiency of circulating and hippocampal insulin-like growth factor I induces depressive behavior in adult mice: a potential model of geriatric depression

et al. 2011

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“…Additionally, in males, the role of testicular hormones is usually disregarded simply because it is relatively constant and decreases linearly with age. However, the literature reveals that aged male rats and men, when compared with young adults, respond less well to antidepressant treatments [116, 117]. Thus, the optimal sex comparison in the response to antidepressants must consider aged-matched populations.…”

Section: Sex and Age Differences In Affective Disorders And Their Trementioning

confidence: 99%

Sex, Stress, and Mood Disorders: At the Intersection of Adrenal and Gonadal Hormones

et al. 2012

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The risk for neuropsychiatric illnesses has a strong sex bias, and for major depressive disorder (MDD), females show a more than 2-fold greater risk compared to males. Such mood disorders are commonly associated with a dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis. Thus, sex differences in the incidence of MDD may be related with the levels of gonadal steroid hormone in adulthood or during early development as well as with the sex differences in HPA axis function. In rodents, organizational and activational effects of gonadal steroid hormones have been described for the regulation of HPA axis function and, if consistent with humans, this may underlie the increased risk of mood disorders in women. Other developmental factors, such as prenatal stress and prenatal overexposure to glucocorticoids can also impact behaviors and neuroendocrine responses to stress in adulthood and these effects are also reported to occur with sex differences. Similarly, in humans, the clinical benefits of antidepressants are associated with the normalization of the dysregulated HPA axis, and genetic polymorphisms have been found in some genes involved in controlling the stress response. This review examines some potential factors contributing to the sex difference in the risk of affective disorders with a focus on adrenal and gonadal hormones as potential modulators. Genetic and environmental factors that contribute to individual risk for affective disorders are also described. Ultimately, future treatment strategies for depression should consider all of these biological elements in their design.

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“…Second, the relatively short duration of two weeks of CMS before the treatment regime, or the drug intervention launched at the same time of CMS, apparently does not parallel clinical situation in which patients usually suffer from the stressors long before they can be treated. Third, the age of rats entering the CMS program is crucial for mediating the drug effects (15); however, the majority of evidences so far obtained were from rats entering the paradigm at their preadolescent age (30,32,34,39). Last but not the least, since rat strain is a determinant for sensitivity of the CMS model (2), it is interesting to have an idea of what would happen in rats of lower CMS sensitivity, yet which would endure a longer duration of CMS.…”

Section: Introductionmentioning

confidence: 99%

Effects of Escitalopram on a Rat Model of Persistent Stress-Altered Hedonic Activities: Towards a New Understanding of Stress and Depression

et al. 2015

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Chronic mild stress (CMS) paradigm is a model to simulate clinical depression induced by long-term environmental stress. The present study investigated the effects of escitalopram, a specific serotonin reuptake inhibitor (SSRI), on depression-like activities in adult (18 week-old) Sprague-Dawley (SD) rats that underwent a total 8-week CMS. Body weight, locomotor activity and sucrose consumption of the rats were measured under CMS paradigm and following escitalopram treatment. The plasma level of corticosterone was also measured at the end of the experiment. Our results revealed that the CMS program reduced the body weight, but not the locomotor activity of the rats. Adult SD rats consumed less sucrose solution under CMS. However, chronic escitalopram regime (10 mg/kg/day for 4 weeks) appeared not helpful in reversing this CMS effect and, if any, the drug exaggerated anxiety profile of the animals. Unexpectedly, the stressed rats exhibited higher sucrose consumption than non-stressed rats after receiving repeated saline injections. Further, the stressed rats were found to have a higher plasma level of corticosterone after escitalopram treatment. Our results provide an example of the possibility that previously stressed individuals may develop an anti-depression ability that lessens the benefits of intervention with antidepressants. Finally, a separate group of rats that entered the CMS program at 10 week-old were used to examine possible effects of aging to interpret the stress coping ability observed in the 18 week-old rats. The younger rats developed less anti-anhedonia effects under repeated saline injections. The data of the present study provide a different perspective on stress-induced depression and possible interaction with antidepressants.

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Aging impairs the antidepressant-like response to citalopram in male rats

Cited by 22 publications

References 33 publications

Long-term deficiency of circulating and hippocampal insulin-like growth factor I induces depressive behavior in adult mice: a potential model of geriatric depression

Long-term deficiency of circulating and hippocampal insulin-like growth factor I induces depressive behavior in adult mice: a potential model of geriatric depression

Sex, Stress, and Mood Disorders: At the Intersection of Adrenal and Gonadal Hormones

Effects of Escitalopram on a Rat Model of Persistent Stress-Altered Hedonic Activities: Towards a New Understanding of Stress and Depression

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