Polycystic ovarian syndrome (PCOS) is characterised by androgen excess, infertility and insulin resistance often leading to a culmination of one or more secondary conditions including hirsutism and obesity. Advances into the pathophysiology of PCOS have been slow due to its heterogeneous nature and lack of a suitable animal model. Cognitive function in PCOS patients has received little attention. The antiprogesterone (AP) treated rat may be a suitable pre-clinical model, showing very similar endocrine and morphological changes to women with PCOS. This study aims to evaluate cognitive function in the AP treated rat using the novel object recognition task.

21 mature female hooded-Lister rats (250±10g) were group housed under standard laboratory conditions. ORG31710 (Mizutani et al., 1992) at 10 & 20 mg/kg, s.c or vehicle (olive oil, 1ml/kg, s.c) was administered once daily for 8 days. On day 4 animals were tested in the novel object recognition task (Grayson & Neill, 2004). Te sting consisted of a 3-min acquisition phase where rats explored two identical novel objects followed by a 1-h inter-trial interval, when rats were returned to the home cage. Finally in the retention trial, rats explored a familiar (duplicate from first trial) and a novel object for 3 mins. Object exploration is defined by rats licking, sniffing, or touching the object with forepaws whilst sniffing. The exploration time (s) of each object in each trial was recorded. Data are expressed as the mean ± SEM (n = 7 per group) and analysed by paired sample’s t-test.

There was no difference in exploration time (s) of the two familiar objects in the acquisition trial for any treatment group. ORG31710, significantly increased exploration of the novel compared with the familiar object (Table 1).

Table 1. The ability of sub-chronic ORG31710 to enhance short-term working memory.

***p<0.001 & **p<0.01: novel compared to familiar object exploration for that treatment group.

These results suggest that the AP agent, ORG31710, may enhance working memory. There is some evidence to link this enhancement to an increase in circulating testosterone (Bimonte-Nelson et al. 2003), however this may be due to conversion of testosterone to estradiol by aromatase. Conversely glucose disregulation due to states like type two diabetes mellitus, seen in PCOS, is associated with cognitive impairments (Messier et al., 2003). In conclusion these results support a role for gonadal steroids in cognitive function and investigation is required.

Bimonte-Nelson, H.A et al., (2003) Experimental Neurology 181, 301-312.
Grayson B and Neill J.C (2004) J. Psychopharmacology 18, A55.
Messier, C. et al., (2003) Neurobiology of Aging 24, 985-1003.
Mizutani., et al., (1992) J. Steroid Biochemical and Molecular Biology 42, 695-704.

The authors wish to thank Organon, NV for their generous donation of compound ORG31710.