Estrous cycle and sex differences in performance on anxiety tasks coincide with increases in hippocampal progesterone and 3α,5α-THP

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Abstract

Sex differences and estrous cycle variations in anxiolytic-like behaviors and progestin concentrations were examined. Proestrous (n=22), estrous (n=19), diestrous (n=20), and male (n=18) Long–Evans rats were tested in horizontal crossing, open field, elevated plus-maze, emergence, holeboard, social interaction, tailflick, pawlick, and defensive burying tasks. Concentrations of plasma and hippocampal progesterone and 5α-pregnan-3α-ol-20-one (3α,5α-THP) were measured by radioimmunoassay in behaviorally tested (proestrus n=11, estrus n=8, diestrus n=9, male n=7) and yoked non-tested rats (proestrus n=11, estrus n=8, diestrus n=10, male n=8). Proestrous females exhibited more anxiolytic-like behavior than all other groups on the elevated plus-maze, social interaction, and defensive burying tasks. Proestrous females had significantly shorter latencies to emerge from a cylinder than did estrous and diestrous females, but not males. Proestrous and estrous females entered significantly more peripheral and total squares in a brightly-lit open field than did males. While proestrous females had a tendency to make more beam breaks than did males in the horizontal crossing task, there were no differences between groups on the holeboard task. There was a tendency for proestrous females to have longer tailflick latencies than diestrous and male rats; however, on the pawlick task there were no differences among the groups. Plasma and central progesterone and 3α,5α-THP of tested and non-tested rats were not different. Proestrous females had significantly higher plasma and hippocampal progesterone and 3α,5α-THP levels than all other groups. These data demonstrate that proestrous increases in anxiolytic-like behavior coincide with elevated circulating and hippocampal progestin concentrations.

Section snippets

Method

These methods were pre-approved by the Institutional Animal Care and Use Committee.

Horizontal crossings

There was a tendency for proestrous females to make more beam breaks in the horizontal crossing task than males [F(3,75)=2.271, P<.087; see Table 1].

Open field

The proestrous and estrous females entered significantly more peripheral [F(3,75)=3.082, P<.03; see Fig. 1] and total squares [F(3,75)=3.456, P<.03] than did males. There was no significant difference between groups in the total number of central squares entered. The average number of central squares entered by each group was proestrus 33 (±4),

Discussion

Proestrous females exhibited more anxiolytic-like behavior than other groups on some, but not all, of the tasks and had significantly higher hippocampal and plasma progesterone and 3α,5α-THP levels than did all other females and males. The increased anxiolytic-like behavior of the proestrous rats, compared to all other groups, was demonstrated by significantly more open arm entries and time in the elevated plus-maze, longer social interactions with conspecifics, and less freezing time in

Acknowledgements

This research was supported by grants from The Whitehall Foundation (96-10) and by the National Science Foundation (95-14463; 98-96263). We thank Dr. Robert Rosellini for his assistance with the horizontal crossing and defensive burying techniques.

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