Chronic oral treatment with 13-cis-retinoic acid (isotretinoin) or all-trans-retinoic acid does not alter depression-like behaviors in rats.
Oral treatment with the anti-acne drug Accutane (isotretinoin, 13-cis-retinoic acid) has been associated with suicide ideation and depression. Here, depression-like behaviors (i.e., behavioral despair and anhedonia) were quantified in adult Sprague-Dawley rats gavaged daily beginning at postnatal day (PND) 82 with 13-cis-RA (7.5 or 22.5 mg/kg) or all-trans-retinoic acid (10 or 15 mg/kg ). Tested at PND 130-131 in the Forced Swim Test, 7.5 mg/kg 13-cis-RA marginally decreased immobility and slightly increased climb/struggle durations whereas neither all-trans-retinoic acid group differed from controls. Voluntary saccharin solution (0.03%) intake at PND 102-104 and PND 151-153 was not different from controls in any treated group, although all RA-treated groups had lower intakes. Swim speed in a water maze at PND 180 was similar across groups, indicating no RA-induced differences in physical ability. Open field activity was mildly decreased at PND 91 in 7.5 mg/kg-treated males only, but it was within the control range at PND 119, 147, and 175. Thus, at serum levels similar to those in humans receiving the drug, chronic 13-cis-RA treatment did not severely affect depression-like behaviors in rats. These data do not substantiate the hypothesis of 13-cis-RA-induced depression.
Ferguson
Sherry A
SA
Division of Neurotoxicology, National Center for Toxicological Research/US Food and Drug Administration, Jefferson, Arkasas 72079, USA. sferguson@ncte.fda.gov
Cisneros
F Javier
FJ
Gough
B
B
Hanig
Joseph P
JP
Berry
Kimberly J
KJ
D000375:Aging / Q000523:psychology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D003863:Depression / Q000523:psychology*; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005260:Female; D015474:Isotretinoin / Q000633:toxicity*; D007641:Keratolytic Agents / Q000633:toxicity*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D012439:Saccharin; D012727:Sex Characteristics; D013549:Sweetening Agents; D013550:Swimming / Q000523:psychology; D014212:Tretinoin / Q000633:toxicity*
D007641:Keratolytic Agents; D013549:Sweetening Agents; D014212:Tretinoin; D015474:Isotretinoin; D012439:Saccharin