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Oral treatment with ACCUTANE does not increase measures of anhedonia or depression in rats.
Neurotoxicol Teratol. 2007 Nov-Dec; 29(6):642-51.NT

Abstract

Reports of depression and/or suicide with ACCUTANE (13-cis-retinoic acid (13-cis-RA)) use prompted studies in a rodent model to ascertain its potential effects. Previously, there were no effects on measures of anhedonia (intake of a saccharin-flavored solution) and depression (forced swim test (FST) behaviors) in rats treated with 7.5 or 22.5 mg/kg 13-cis-RA [S.A. Ferguson, F.J. Cisneros, B. Gough, J.P. Hanig, K.J. Berry, Chronic oral treatment with 13-cis-retinoic acid (isotretinoin) or all-trans-retinoic acid does not alter depression-like behaviors in rats, Toxicol. Sci. 87 (2005) 451-459.]. Here, dose and temporal thresholds were investigated by increasing the maximum 13-cis-RA dose to 30 mg/kg, extending treatment duration, and measuring behaviors repeatedly. Beginning on post-natal day 59, male and female Sprague-Dawley rats were gavaged with soybean oil, 7.5 or 30 mg/kg/day of 13-cis-RA for approximately 19 weeks. FST behaviors were measured after 24, 82, and 131 treatment days and saccharin intake (0.03% solution) was measured at baseline and after 14, 35, 56, and 112 treatment days. Body weight and food intake were not altered by treatment. FST durations of swim, climb/struggle, and immobility were unaffected by 13-cis-RA at any time during treatment. More males than females required "rescue" in the FST but there was no treatment effect on number of rats requiring early removal. 13-cis-RA treatment had no effects on saccharin intake at any time. Given that the 7.5 mg/kg dose produces serum levels which parallel those of humans [S.A. Ferguson, P.H. Siitonen, F.J. Cisneros, B. Gough, J.F. Young, Steady state pharmacokinetics of oral treatment with 13-cis-retinoic acid or all-trans-retinoic acid in male and female adult rats, Basic Clin. Pharmacol. Toxicol 98 (2006) 582-587.], these results are quite relevant. Combined with previous results, these results provide further evidence that 13-cis-RA does not produce behavioral alterations indicative of depression in rats.

Authors+Show Affiliations

Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR 72079 USA. Sherry.Ferguson@fda.hhs.govNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17933491

Citation

Ferguson, Sherry A., et al. "Oral Treatment With ACCUTANE Does Not Increase Measures of Anhedonia or Depression in Rats." Neurotoxicology and Teratology, vol. 29, no. 6, 2007, pp. 642-51.
Ferguson SA, Cisneros FJ, Hanig JP, et al. Oral treatment with ACCUTANE does not increase measures of anhedonia or depression in rats. Neurotoxicol Teratol. 2007;29(6):642-51.
Ferguson, S. A., Cisneros, F. J., Hanig, J. P., & Berry, K. J. (2007). Oral treatment with ACCUTANE does not increase measures of anhedonia or depression in rats. Neurotoxicology and Teratology, 29(6), 642-51.
Ferguson SA, et al. Oral Treatment With ACCUTANE Does Not Increase Measures of Anhedonia or Depression in Rats. Neurotoxicol Teratol. 2007 Nov-Dec;29(6):642-51. PubMed PMID: 17933491.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oral treatment with ACCUTANE does not increase measures of anhedonia or depression in rats. AU - Ferguson,Sherry A, AU - Cisneros,F Javier, AU - Hanig,Joseph P, AU - Berry,Kimberly J, Y1 - 2007/09/18/ PY - 2007/05/10/received PY - 2007/09/05/revised PY - 2007/09/06/accepted PY - 2007/10/16/pubmed PY - 2008/2/26/medline PY - 2007/10/16/entrez SP - 642 EP - 51 JF - Neurotoxicology and teratology JO - Neurotoxicol Teratol VL - 29 IS - 6 N2 - Reports of depression and/or suicide with ACCUTANE (13-cis-retinoic acid (13-cis-RA)) use prompted studies in a rodent model to ascertain its potential effects. Previously, there were no effects on measures of anhedonia (intake of a saccharin-flavored solution) and depression (forced swim test (FST) behaviors) in rats treated with 7.5 or 22.5 mg/kg 13-cis-RA [S.A. Ferguson, F.J. Cisneros, B. Gough, J.P. Hanig, K.J. Berry, Chronic oral treatment with 13-cis-retinoic acid (isotretinoin) or all-trans-retinoic acid does not alter depression-like behaviors in rats, Toxicol. Sci. 87 (2005) 451-459.]. Here, dose and temporal thresholds were investigated by increasing the maximum 13-cis-RA dose to 30 mg/kg, extending treatment duration, and measuring behaviors repeatedly. Beginning on post-natal day 59, male and female Sprague-Dawley rats were gavaged with soybean oil, 7.5 or 30 mg/kg/day of 13-cis-RA for approximately 19 weeks. FST behaviors were measured after 24, 82, and 131 treatment days and saccharin intake (0.03% solution) was measured at baseline and after 14, 35, 56, and 112 treatment days. Body weight and food intake were not altered by treatment. FST durations of swim, climb/struggle, and immobility were unaffected by 13-cis-RA at any time during treatment. More males than females required "rescue" in the FST but there was no treatment effect on number of rats requiring early removal. 13-cis-RA treatment had no effects on saccharin intake at any time. Given that the 7.5 mg/kg dose produces serum levels which parallel those of humans [S.A. Ferguson, P.H. Siitonen, F.J. Cisneros, B. Gough, J.F. Young, Steady state pharmacokinetics of oral treatment with 13-cis-retinoic acid or all-trans-retinoic acid in male and female adult rats, Basic Clin. Pharmacol. Toxicol 98 (2006) 582-587.], these results are quite relevant. Combined with previous results, these results provide further evidence that 13-cis-RA does not produce behavioral alterations indicative of depression in rats. SN - 0892-0362 UR - https://www.unboundmedicine.com/medline/citation/17933491/Oral_treatment_with_ACCUTANE_does_not_increase_measures_of_anhedonia_or_depression_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0892-0362(07)00324-8 DB - PRIME DP - Unbound Medicine ER -