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  • Eltrombopag Olamine Impulsive burying and freezing behaviors


    Impulsive burying and freezing behaviors in response to aversive stimuli may represent attempts to avoid novel and/or aversive stimuli. These behaviors can be assessed utilizing the marble burying and conditioned fear tasks, respectively. For example, Wistar rats in proestrus and ovariectomized rats bury fewer marbles when exposed to red light and white noise than those in metestrus do (Schneider and Popik, 2007). These findings suggest that steroids may influence the expression of burying behavior. Ovariectomized rats administered systemic progesterone and/or estrogen spend less time freezing after they touch a shock-associated prod compared to vehicle-administered controls (Frye and Walf, 2004). Effects of progesterone in the conditioned fear paradigm can be utilized to assess avoidant behaviors related to contextual aversive stimuli. Progesterone and/or estrogen\'s ability to mediate freezing behaviors of female rats in response to re-exposure to stimuli associated with aversive stimuli, such as a tone associated with a shock in the conditioned fear paradigm, has not been systematically investigated. Because steroid hormones have been implicated in mediating sex differences in affective processes, it is important to elucidate their effects on avoidance of aversive stimuli. Thus, we conducted experiments to examine the mediating effects of progesterone and/or estrogen on impulsive and avoidant behaviors of intact and ovariectomized rats.
    Discussion Results of the present study supported our hypothesis that estrous Eltrombopag Olamine and P4 and/or E2 administration to ovx rats would influence impulsivity and freezing behavior. Rats in behavioral estrous spent significantly less time burying marbles than did diestrous rats. As well, rats in behavioral estrous spent less time freezing when in a contextual situation associated with shock than did diestrous rats. Rats in behavioral estrous had elevated P4, E2 and 3α,5α-THP levels in plasma, and higher P4 and E2 levels in cortex, compared to diestrous rats. Furthermore, rats in behavioral estrous had elevated 3α,5α-THP and E2 levels in hippocampus compared to diestrous rats. Ovx rats administered P4 or E2+P4 spent less time burying marbles than did rats administered vehicle or E2. As well, P4 administration decreased freezing when there was contextual association with a shock. Rats administered P4, E2 or both had a significant increase in P4 levels in cortex compared to rats administered vehicle. As well, rats administered E2+P4 had higher levels of 3α,5α-THP in hippocampus and rats administered P4 or E2+P4 had higher levels of P4 and 3α,5α-THP in plasma compared to rats administered vehicle. Rats administered E2 or E2+P4 had higher levels of E2 in hippocampus as well. There were behavioral differences during diestrous and behavioral estrous, when E2 and P4 levels are low and high, respectively. Moreover, administration of P4 to ovx rats produced similar patterns of behavior, as was observed in rats in behavioral estrous. This implies that progestogens and/or estrogens may be important hormonal factors that contribute to marble burying, an index of impulsivity, and freezing, a measure of conditioned fear behaviors. Our findings confirm and extend previous observations regarding endogenous and exogenous effects of progestogens and/or estrogens on impulsive burying in this model. Previous findings demonstrate Wistar rats in proestrus buried fewer marbles (~2.7 marbles) than did those in metestrus (~3.5 marbles), and ovx rats demonstrated burying behavior (~2.6 marbles) similar to proestrous rats (Schneider and Popik, 2007). Our findings extend this work to demonstrate the sensitivity of other measures in the marble burying task. Long–Evans rats in behavioral estrous spent less time burying marbles than did diestrous rats, and ovx rats administered P4 or both P4 and E2 spent less time burying marbles than did rats administered E2 or vehicle. Although there were differences in the duration of time rats spent burying marbles, there was no significant differences in the number of marbles buried by diestrous, behavioral estrous, ovx, P4 and/or E2,or vehicle-administered rats. In our hands, the lack Eltrombopag Olamine of effect on the number of marbles buried may be attributable to the more stringent burying criteria we utilized (the entire marble, rather than half of it, had to be covered to be considered buried) and/or potential differences between rat strains (we used Long–Evans rats but the earlier investigation was in Wistar rats) in sensitivity to progestogens and/or estrogens.