Oral Accutane® (13- cis-retinoic acid) has no effects on spatial learning and memory in male and female Sprague-Dawley rats

Abstract

Descriptions of psychiatric effects with Accutane® (13- cis-retinoic acid (13- cis-RA)) use prompted a series of studies in a rodent model to ascertain its cognitive effects. Previously, we reported no effects on measures of anhedonia and depression in rats treated with 7.5, 22.5, or 30 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 [16]; S.A. Ferguson, F.J., Cisneros, J.P. Hanig, K.J. Berry, Chronic oral treatment with Accutane (13- cis-retinoic acid) does not increase measures of anhedonia or depression in male and female Sprague-Dawley rats, (in preparation) [19]]. Here, we assessed spatial learning and memory in male and female Sprague-Dawley rats gavaged daily beginning on postnatal day (PND) 59 with vehicle control (soybean oil), 7.5 or 30 mg/kg of 13- cis-RA. We have reported that 7.5 mg/kg produces serum levels of 13- cis-RA comparable to those of humans prescribed Accutane® [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 [18]]. Three behavioral tasks assessed spatial learning and memory after chronic 13- cis-RA treatment: the escape-reinforced Morris water maze (PNDs 111–115), the food-reinforced 8-arm radial maze (PNDs 132–136), and the water-reinforced NCTR complex maze (PNDs 153–157). Behaviors were measured after a minimum of 52 and maximum of 94 days of 13- cis-RA treatment. 13- cis-RA treatment had no effects on performance of the 8-arm radial maze or the NCTR complex maze. Treatment effects on Morris water maze performance were negligible and neither dose-related nor consistent. Performances of the control group were quite similar to those previously described in this laboratory. These results indicate that chronic 13- cis-RA treatment in male and female rats has few effects on measures of spatial learning and memory.