Oral treatment with ACCUTANE® does not increase measures of anhedonia or depression in rats

Ferguson, Sherry A.; Cisneros, Francisco Javier Barbancho; Hanig, Joseph P.; Berry, Kimberly J.

doi:10.1016/j.ntt.2007.09.003

Cited by 22 publications

(11 citation statements)

References 72 publications

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“…22 These changes were not seen in adult rats. 27 In 13 humans, isotretinoin decreased orbitofrontal cortex metabolism, but this decrease was not accompanied by an increase in the severity of depression. 28 Limitations and strengths of study Our study has some limitations.…”

Section: Discussionmentioning

confidence: 98%

“…This indicates that they Several studies have shown that the molecular components needed for retinoic acid signalling are expressed in the adult brain, suggesting that retinoids could play a role in affective disorders. [21][22][23][24][25][26][27][28][29] In young adult mice, chronic administration of isotretinoin induced depression related behaviours. 22 These changes were not seen in adult rats.…”

Section: Discussionmentioning

confidence: 99%

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Association of suicide attempts with acne and treatment with isotretinoin: retrospective Swedish cohort study

Sundström

Alfredsson

Sjölin‐Forsberg

et al. 2010

BMJ

167

126

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An increased risk of attempted suicide was apparent up to six months after the end of treatment with isotretinoin, which motivates a close monitoring of patients for suicidal behaviour for up to a year after treatment has ended. However, the risk of attempted suicide was already rising before treatment, so an additional risk due to the isotretinoin treatment cannot be established. As patients with a history of suicide attempts before treatment made new attempts to a lesser extent than did patients who started such behaviour in connection with treatment, patients with severe acne should not automatically have isotretinoin treatment withheld because of a history of attempted suicide.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Association of suicide attempts with acne and treatment with isotretinoin: retrospective Swedish cohort study

Sundström

Alfredsson

Sjölin‐Forsberg

et al. 2010

BMJ

167

126

View full text Add to dashboard Cite

show abstract

“…Similarly, treatment of rats with RA also leads to degradation in performance in learning and memory tests (Dopheide and Morgan 2008) while others have reported an increase in anxiety like behaviour (Cai et al 2010). Despite these multiple effects by RA on the CNS, its influence on depression-like behaviour in the rodent is less clear with several studies pointing to an increase in some depressive-like behaviours (O’Reilly et al 2006; Trent et al 2009) with others studies showing no change (Ferguson et al 2005, 2007). One possible explanation for variation in result between studies is the baseline of RA signalling—RA exhibits a U-shaped curve in its toxicity, with detrimental effects in both deficiency and excess and endogenous levels crucially influence the possible harmful effect of an exogenous dose.…”

Section: Discussionmentioning

confidence: 99%

High expression of retinoic acid receptors and synthetic enzymes in the human hippocampus

et al. 2011

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Retinoic acid, the active form of the nutrient vitamin A, regulates several facets of neuronal plasticity in the hippocampus, including neurogenesis and synaptic strength, acting via specific retinoic acid receptors (RARs). Essential for conversion of vitamin A to retinoic acid is the enzyme retinaldehyde dehydrogenase (RALDH) and in the rodent hippocampus this is only present in the adjacent meninges where it must act as a locally released paracrine hormone. Little is known though about the expression of RALDHs and RARs in the human hippocampus. This study confirms that RALDH levels are very low in mouse neurons but, surprisingly, strong expression of RALDH protein is detected by immunohistochemistry in hippocampal neurons. The receptors RARα, β and γ were also detected, each receptor exhibiting differing subcellular locations implying their potential regulation of both transcription and non-genomic actions. These results imply an essential function of retinoic acid in the human hippocampus likely to include regulation of neuronal plasticity.

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“…Controversially, the use of 13- cis -RA has been reported to increase the incidence of depressive illness in approximately 1-10% of patients receiving the drug (Hull and D’Arcy, 2005, Bremner and McCaffery, 2008). In animal studies chronic administration of 1 mg/kg 13- cis -RA has been shown to increase depression-related behaviours in both mice and rats (O’Reilly et al, 2006, Trent et al, 2009) but not in all studies of the adult rat (Ferguson et al, 2005, 2007). However, the mechanism by which 13- cis -RA treatment can influence depression-related behavioural changes remains poorly understood.…”

Section: Introductionmentioning

confidence: 94%

Chronic administration of 13-cis-retinoic acid does not alter the number of serotoninergic neurons in the mouse raphe nuclei

et al. 2011

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The synthetic retinoid 13-cis-retinoic acid (13-cis-RA), prescribed for the treatment of severe nodular acne, has been linked to an increased incidence of depression. Chronic treatment studies in rodents have shown that 13-cis-RA induces an increase in depression-related behaviours and a functional uncoupling of the hippocampus and dorsal raphe nucleus (DRN). Changes in the number of serotoninergic neurons in the DRN have been reported in depressed human patients. Given that retinoids have apoptotic effects, we hypothesised that a decrease in the number of serotoninergic neurons in the DRN or median raphe nucleus (MRN) would lead to decreased serotoninergic tone and in turn to the behavioural changes seen with 13-cis-RA administration. Here, we used immunolabelling and unbiased stereological methods to estimate the number of serotonin (5-hydroxytryptamine, 5-HT) neurons in the MRN and DRN of vehicle control and 13-cis-RA-treated adult mice. In the MRN, the number of 5-HT immunolabelled cells was 1815 ± 194 in control, compared with 1954 ±111 in 13–cis-RA treated tissues. The number of 5-HT immunolabelled cells was much higher in the DRN, with 7148 ± 377 cells in the control, compared with 7578 ± 424 in the 13-cis-RA treated group. Further analysis of the DRN revealed that there were no changes in the number of 5-HT neurons within distinct subregions of the DRN. Similarly, changes in the density of serotoninergic neurons or in the volume of the MRN or DRN were not observed in 13-cis-RA treated animals. These data show that apoptotic actions of 13-cis-RA do not occur in vivo at drug concentrations that induce changes in depression-related behaviour and functional uncoupling of the DRN and hippocampus. The potential pro-depressant behavioural and molecular effects associated with chronic administration of 13-cis-RA may result from changes in serotoninergic activity rather than changes in the number of serotoninergic neurons.

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Oral treatment with ACCUTANE® does not increase measures of anhedonia or depression in rats

Cited by 22 publications

References 72 publications

Association of suicide attempts with acne and treatment with isotretinoin: retrospective Swedish cohort study

Association of suicide attempts with acne and treatment with isotretinoin: retrospective Swedish cohort study

High expression of retinoic acid receptors and synthetic enzymes in the human hippocampus

Chronic administration of 13-cis-retinoic acid does not alter the number of serotoninergic neurons in the mouse raphe nuclei

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