Performance on a modified signal detection task of attention is impaired in male and female rats following developmental exposure to the synthetic progestin, 17α-hydroxyprogesterone caproate

Abstract

Based on evidence that the developing mesocortical dopamine pathway is sensitive to progestins, in the present study we tested the hypothesis that attention, a fundamental component of successful cognitive behavior, is disrupted by developmental exposure to the synthetic progestin, 17-α-hydroxyprogesterone caproate (17-OHPC). To assess attentional impairments, a modified signal detection task was utilized with three stimulus modalities: compound (light and tone), light alone, and tone alone, for four stimulus durations (2, 0.5, 0.25, 0.125 s). Adult rats were trained to push one lever if they detected the stimulus, and another lever if the stimulus was not presented. 17-OHPC animals were able to attend to the task, as evidenced by similar correct responses as controls. However, as the task became increasingly difficult at shorter durations, 17-OHPC animals made significantly more omissions compared to controls, suggesting that 17-OHPC treatment may disrupt attentional processes and/or delay response time. These findings add to the current body of literature demonstrating that exposure to 17-OHPC during development produces deficits in cognitive behavior in adulthood. These results may inform potential risks associated with 17-OHPC treatment in pregnant women with a history of preterm delivery who are commonly recipients of such treatment.

Keywords: 17-α-hydroxyprogesterone caproate; Attention; Mesocortical dopamine pathway; Omissions.

Fig. 1.

Signal detection task. (A) At baseline, a brief inter-trial interval (ITI) was followed by a 2-second presentation of compound (light and tone) stimuli (signaled trial, top) or no stimuli (unsignaled trial, bottom). 1 s later, the houselight was illuminated, and levers were extended. Rats were rewarded for responding on the right lever in signaled trials, and on the left lever in unsignaled trials. (B) Testing was similar to baseline with trials divided into 3 sessions of 4 blocks each. In each session, signaled trials were indicated by compound (light and tone, left) or simple stimuli (light or tone, right). Within each session, stimulus duration was decreased from 2 s, to 0.5, 0.25, and 0.125 s in subsequent blocks. See Methods for experimental details.

Fig. 2.

Stimulus modality affects performance on attentional measures. Performance as measured by (A) percent correct responses on completed trials, (B) number of pellets earned, and (C) percent trials with omissions in oil and 17-OHPC treated males and females (all groups combined for graph) for the compound stimulus (closed circles), light alone (open circles) or tone alone (closed triangles). Performance for all three measures was lower for the tone stimulus compared to compound or light. Additionally, for all three stimuli, performance on each measure declined as duration decreased. *significant effect P < 0.05.

Fig. 3.

Performance with compound (light and tone) stimulus presentation. Performance as measured by (A, D) percent correct responses (B, E) number of pellets earned, and (C, F) percent trials with omissions in oil (closed circles) and 17-OHPC (open circles) treated males and females (combined for graph). Performance differed on signaled and unsignaled trials. In the signaled trials, there were no treatment differences in percent correct (A) or pellets (B), but there was a treatment effect on omissions (C). In the unsignaled trials, 17-OHPC treated animals made more correct responses (D) and earned more pellets (E) than controls at 0.5 s. There were no treatment differences on percent omissions (F). *significant effect P < 0.05.

Fig. 4.

Performance with light stimulus presentation. Performance as measured by (A, D, G) percent correct responses, (B, E, H) number of pellets earned, and (C, F, I) percent omissions in oil (closed circles) and 17-OHPC (open circles) treated males and females (combined for graphs A–F). Performance differed on signaled and unsignaled trials. In the signaled trials, there was a sex × treatment interaction in percent correct responses (G) and pellets earned (H), and a treatment effect on percent omissions (C). In the unsignaled trials, there was a sex × treatment interaction in percent omissions (I). **significant effect P < 0.05; * significantly different than control females (P < 0.05); ≠ significantly different than 17-OHPC females (P < 0.05); #significantly different than control males (P < 0.05).

Fig. 5.

Performance with tone stimulus presentation. Performance as measured by (A, D) percent correct responses (B, E) number of pellets earned, and (C, F) percent trials with omissions in oil (closed circles) and 17-OHPC (open circles) treated males and females (combined for graph). Performance differed on signaled and unsignaled trials. In the signaled trials, there were no treatment differences in percent correct (A) or pellets earned (B), but there was a main effect of treatment and a duration × treatment interaction (0.125 s) on percent omissions (C). In the unsignaled trials, treatment did not affect percent correct responses (D), however 17-OHPC treated animals earned fewer pellets (E) and made more percent omissions (F) than controls. There was also a duration × treatment interaction, where 17-OHPC animals made significantly more omissions than controls at 0.125 s (F). *significant effect P < 0.05.