Environmental enrichment prevents anxiety-like behavior induced by progesterone withdrawal in two strains of rats

• Progesterone withdrawal (PW) increases anxiety-like behavior in both strains of rats.
• Fluoxetine prevents anxiety-like behavior induced by PW in Wistar Kyoto rats.
• A gradual reduction of progesterone reduces anxiety-like behavior in Wistar rats.
• Environmental enrichment prevents anxiety-like behavior induced by PW.

Stress vulnerability could influence the treatment response to anxiety associated with abrupt hormonal suppression. The present study explored the effects of different treatments on experimental anxiety induced by progesterone withdrawal (PW) in a stress-sensitive rat strain, Wistar Kyoto (WKY), in the burying behavior test (BBT). The following experimental series was conducted using independent groups of Wistar (control strain) and WKY ovariectomized rats: Experiment 1: Rats were treated for 5 days with oil, a constant dose of progesterone (0.5 mg/rat, s.c) or a combination of progesterone (0.5 mg/rat, s.c) plus fluoxetine (10 mg/kg, i.p); on day 6, all rats were subjected to BBT. Experiment 2: Rats received corn oil or decreasing doses of progesterone (0.84, 0.67, 0.5, 0.33 and 0.17 mg/rat; one dose daily); on day 6, the rats were subjected to BBT. Experiment 3: Rats were divided into two groups that were subjected to 30 days of standard conditions or environmental enrichment (EE); from days 25 to 30, all rats received a fixed dose of progesterone (0.5 mg/rat, s.c.) or vehicle. On day 31, the rats were tested with BBT. Results showed that PW increased anxiety in both strains, and fluoxetine prevented anxiety in WKY rats. In contrast, a gradual reduction of progesterone prevents the anxiety in Wistar but not in WKY. EE was preventive against the anxiety induced by PW in both strains of rats. Thus, the results suggest that anxiety induced by PW is prevented by EE while the anxiolytic effect of pharmacological treatments depends on stress vulnerability.