Progestins influence performance on cognitive tasks independent of changes in affective behavior

Abstract

In this study, the effects of progestins on various cognitive and affective tasks were investigated. Ovariectomized rats (N = 72) received subcutaneously 0.0, 4.0, or 8.0 mg/kg of progesterone (P), dihydroprogesterone (DHP), or 5a-pregnan-3a-oI-20-one (3a,5a-THP) suspended in 10% ethanoVsesame oil vlv. For the cognitive tasks (Y-maze, inhibitory avoidance, and object recognition), the subjects were injected after habituation and training trials and were tested 24 h later. For the nociception and affective tasks (open field, elevated plus-maze, and tailflick), the subjects were injected 1 or 24 h before testing. P reduced latencies to the goal arm in the Y-maze, enhanced latencies to the shock-associated side of the inhibitory avoidance chamber, and increased the percentage of time with a novel object. DHP reduced latencies to the goal arm, increased the percentage of correct choices in the Y-maze, and increased crossover latencies in the inhibitory avoidance task. 3a,5a-THP administration enhanced performance in the inhibitory avoidance task. P, DHP, and 3a,5a-THP increased the number of entries into the central squares of a brightly lit open field, open arm time in the elevated plus-maze, and tailflick latencies, when administered 1 h, but not 24 h, prior to testing. These data suggest that some progestins, when administered following habituation and training and 24 h prior to testing, produce changes in cognitive performance that do not coincide with overt changes in the affective behaviors examined.Cognitive changes over endogenous hormone cycles following removal of the ovaries and after hormone replacement suggest that there are activational effects of steroids on cognitive performance. The majority of these studies have focused on estrogen's (E) effects. Systemic E administration to ovariectomized rats (McCord, Hamlin, Pool, & Milner, 1979) and mice (Miele, Rosellini, & Svare, 1988) enhances conditioned aversions and reverses the learning deficits in T-maze performance induced by scopolamine (Dohanich, Fader, & Javorsky, 1994). Intrahippocampal E to ovariectomized rats significantly improves long-term memory retention in a spatial water maze task, as compared with vehicle-administered controls (Packard & Teather, 1997). These studies, and others, provide evidence that E has activational effects on cognitive performance in rodents.Progesterone (P) normally varies with E over endogenous hormonal cycles and may itself have important effects on cognitive performance; however, the effects of

Estrogen and/or Progesterone Administered Systemically or to the Amygdala Can Have Anxiety-, Fear-, and Pain-Reducing Effects in Ovariectomized Rats.

“…Our results, that E 2 + P administered systemically or to the amygdala can reduce pain responsiveness of ovx rats, coincide with previous results that steroid hormones influence nociception (Berkley, 1997) and that the amygdala may be a substrate for these responses. Systemic or intracerebroventricular administration of progestins to female rodents can decrease pain responsiveness (Frye & Duncan, 1994, 1996; Frye & Lacey, 2000; Kavaliers & Wiebe, 1987; Wiebe & Kavaliers, 1988). Coadministration of E 2 and/or P increases latencies to respond to noxious stimuli when administered systemically (Frye & Lacey, 2000; Gordon & Soliman, 1996).…”

“…Systemic or intracerebroventricular administration of progestins to female rodents can decrease pain responsiveness (Frye & Duncan, 1994, 1996; Frye & Lacey, 2000; Kavaliers & Wiebe, 1987; Wiebe & Kavaliers, 1988). Coadministration of E 2 and/or P increases latencies to respond to noxious stimuli when administered systemically (Frye & Lacey, 2000; Gordon & Soliman, 1996). As well, these data confirm previous reports that have suggested that the amygdala is a substrate for affect and pain.…”

Diverse modulatory effects of sex steroids on depressive-like behavior in socially stressed female rats.

“…In fact, both human and animal studies have indicated that PROG may have a dual effect on anxiety, with the direct effect of PROG being associated with an anxiogenic action (Ladisich, 1974; van Wingen et al, 2008). However, a delayed increase in PROG metabolism can exert an anxiolytic effect, probably mediated by its metabolites (Frye & Lacey, 2000; Mora et al, 1996; Rhodes & Frye, 2001).…”