Antidepressant-like effects of pregnancy and progesterone in Wistar rats as measured in the differential reinforcement of the low-rate 72 s task

Molina-Hernández, Miguel; Contreras, Carlos M.; Téllez-Alcántara, P.

doi:10.1007/s002130000496

Cited by 18 publications

(8 citation statements)

References 28 publications

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“…Experiment 1a determined that three days of PWD was required to detect a significant increase in FST immobility. This finding is consistent with recent reports of delayed increases in FST immobility following steroid withdrawal (Bekku et al, 2007;Stoffel & Craft, 2004), and of increased depression-like behavior in rats at three days postpartum, as assessed in the differential reinforcement of low response-rate model of depression (Molina-Hernández et al, 2000). In the case of Stoffel and Craft (2004), rats received progesterone and estradiol injections, separately or in combination, for a period of more than three weeks.…”

supporting

confidence: 92%

“…These bidirectional manipulations of ALLO levels provide evidence for an inverse relationship between ALLO levels and FST immobility, albeit not in the context of PWD. In contrast, the efforts of other researchers (e.g., Bekku et al, 2007;Molina-Hernández et al, 2000) have reported depression-like effects of PWD, but without specifically assessing potential mechanisms underlying the effect. Thus, FST immobility was previously studied in the context of acute ALLO manipulation or progesterone withdrawal, and the current research combines these lines of research.…”

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confidence: 91%

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Inhibition of progesterone metabolism mimics the effect of progesterone withdrawal on forced swim test immobility

Beckley¹,

Finn²

2007

Pharmacology Biochemistry and Behavior

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Withdrawal from high levels of progesterone in rodents has been proposed as a model for premenstrual syndrome or postpartum depression. Forced swim test (FST) immobility, used to model depression, was assessed in intact female DBA/2J mice following progesterone withdrawal (PWD) or treatment with the 5α-reductase inhibitor finasteride. Following 5 daily progesterone injections (5 mg/kg IP) FST immobility increased only in mice withdrawn for 3 days (p < .05). In another experiment, 3 days of PWD significantly decreased levels of progesterone compared to 0 days of withdrawal, but progesterone levels at 3 days of PWD did not differ from vehicle-treated controls. In a final study, mice received daily injections of progesterone (5 mg/kg IP) for 8 days, with 0 mg/ kg, 50 mg/kg, or 100 mg/kg finasteride co-administered for the last three days. Mice that received 100 mg/kg finasteride, but not 50 mg/kg finasteride, displayed increased FST immobility. PWD and finasteride treatment, both of which reduce allopregnanolone levels, were associated with increased FST immobility in female DBA/2J mice. These findings suggest that decreased levels of the GABAergic neurosteroid allopregnanolone contributes to symptoms of PWD. Future studies of PWD may provide information about human conditions that are associated with hormone changes such as premenstrual syndrome or postpartum depression. KeywordsDepression; premenstrual syndrome; postpartum depression; progesterone withdrawal; behavioral despair; GABA-A receptor; allopregnanolone; finasteride Beginning in adolescence, females experience affective disorders at higher rates than males, partially due to sex-specific disorders such as premenstrual syndrome (PMS) and postpartum depression (McGrath et al., 1990,Steiner et al., 2003. Progesterone secretion is dramatically reduced prior to menstruation or following childbirth. These periods of progesterone clearance have been called "progesterone withdrawal" (PWD), and are associated with dynamic (but species-dependent) biological events in females (MacDonald et al., 1991). Given the temporal Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. association between PWD and PMS or postpartum depression, studies that elucidate the effects of PWD may lead to increased understanding of these disorders. NIH Public AccessEmerging evidence about the cellular actions of progesterone and its metabolites in the brain has stimulated research regarding neuroendocrine correlates of behaviors. In addition to the actions of progesterone on intracellular and membrane-bound receptors, progesterone can be metaboli...

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confidence: 92%

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confidence: 91%

Inhibition of progesterone metabolism mimics the effect of progesterone withdrawal on forced swim test immobility

Beckley¹,

Finn²

2007

Pharmacology Biochemistry and Behavior

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“…For example, proestrous or pregnant rats that have higher levels of steroid hormones show less depressive behavior in the FST than do diestrous, post-partum or male rats that have lower level of hormones (Frye and Walf, 2002, 2004; Walf et al, 2006). Further, in the differential reinforcement model of depression, depressive behavior is increased among rats 3 days postpartum, which should have lower and transitioning levels of steroid hormones (Molina-Hernández et al, 2000). Although these findings imply that depressive behavior is greater when hormone levels are low, there are variations in both estrogens and progestogens, which make it difficult to attribute variations in behavior to hormonal status.…”

Section: Discussionmentioning

confidence: 99%

Progesterone attenuates depressive behavior of younger and older adult C57/BL6, wildtype, and progesterone receptor knockout mice

Frye

2011

Pharmacology Biochemistry and Behavior

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Progesterone may have actions independent of intracellular progestin receptors (PRs) to influence depressive behavior. To investigate this, we examined effects of progesterone (P; 10 mg/kg, SC) on the depressive behavior of mice in the forced swim test (FST). In Experiment 1, subjects were 4 to 6 months old, intact or ovariectomized (OVX) female and intact or gonadectomized (GDX) male, C57/BL6 mice. Progesterone reduced depressive behavior of young diestrous and OVX mice but male mice were impervious to effects of P. In Experiment 2, subjects were intact aged (20–28 months old) C57/BL6 female and male mice. Progesterone reduced depressive behavior of aged female and male C57/BL6 mice, albeit effects were greater among males. In Experiment 3, effects of P were examined in 4 to 6 months old, gonadally-intact, female and male mice that were wildtype or PR knockouts (PRKOs). Progesterone decreased depressive behavior of young adult, wildtype and PRKO mice, which showed greater immobility than did their wildtype counterparts. In Experiment 4, subjects were 18–24 months old wildtype or PRKO mice (Exp 4). Progesterone decreased immobility among wildtype and PRKO mice (which were not different in terms of their baseline depressive behavior). Together these data demonstrate that P decreases depressive behavior of young and older adult C57/BL6, wildtype and PRKO mice, which suggest that acute anti-depressant effects of P may occur independent of actions at “classic” PRs.

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“…This effect can be abolished by removal of circulating ovarian steroids, such that ovariectomized females perform equally to intact and castrated males, which did not differ from each other (Beatty 1973). Pregnancy and replacement Choline effects on time, emotion, and memory of progesterone to ovariectomized females rats improves their DRL efficiency, suggesting that the efficient DRL-schedule performance of female rats can be attributed, in part, to circulating progesterone (e.g., Molina-Hernandez et al 2000). The current finding that the SUP-female rats were even more efficient when acquiring longer DRL criterion times (e.g., 36 and 72 sec) implies that there is an interaction between prenatal-choline supplementation and gonadal hormones, possibly estrogen or progesterone, in female rats (Ross and Santi 2000).…”

Section: Discussionmentioning

confidence: 99%

Prenatal choline supplementation alters the timing, emotion, and memory performance (TEMP) of adult male and female rats as indexed by differential reinforcement of low-rate schedule behavior

Cheng¹,

MacDonald²,

Williams³

et al. 2008

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Choline availability in the maternal diet has a lasting effect on brain and behavior of the offspring. To further delineate the impact of early nutritional status, we examined effects of prenatal-choline supplementation on timing, emotion, and memory performance of adult male and female rats. Rats that were given sufficient choline (CON: 1.1 g/kg) or supplemental choline (SUP: 5.0 g/kg) during embryonic days (ED) 12-17 were trained with a differential reinforcement of low-rate (DRL) schedule that was gradually transitioned through 5-, 10-, 18-, 36-, and 72-sec criterion times. We observed that SUP-females emitted more reinforced responses than CON-females, which were more efficient than both groups of males. In addition, SUP-males and SUP-females exhibited a reduction in burst responding (response latencies <2 sec) compared with both groups of CON rats. Furthermore, despite a reduced level of burst responding, the SUP-males made more nonreinforced responses prior to the DRL criterion as a result of maintaining the previous DRL criterion following transition to a new criterion. In summary, long-lasting effects of prenatal-choline supplementation were exhibited by reduced frustrative DRL responding in conjunction with the persistence of temporal memory in SUP-males and enhanced temporal exploration and response efficiency in SUP-females.Choline is an essential nutrient for the regulation of cell signaling, methyl metabolism, and acetylcholine synthesis in both the infant and adult (Zeisel and Niculescu 2006). It has been found that when choline is administered at levels higher than normal to pregnant rats during embryonic days (ED) 12-17, the adult offspring showed enhanced spatial and temporal memory (Meck and Williams 2003). Specifically, rats given this prenatal-choline supplementation made fewer errors when tested on a radial-arm maze (Meck et al. , 1989Meck and Williams 1999) and are able to chunk more information in spatial memory that helps them identify multiple-reward baiting patterns (Dallal and Meck 1990;Meck and Williams 1997b). Similarly, when challenged with tasks that require the ability to remember durations in the seconds-to-minutes range, prenatal choline-supplemented rats produced more precise timing functions and are better able to time multiple durations simultaneously compared with control rats (Meck and Williams 1997a,c;Cheng et al. 2006b). The prenatal availability of choline also modifies the development of the cholinergic system (e.g., Meck et al. 1989;Williams et al. 1998;Cermak et al. 1999;Montoya et al. 2000;Mellott et al. 2004) and alters indices of hippocampal plasticity (e.g., Pyapali et al. 1998;Glenn et al. 2007). Together, these findings indicate that prenatal-choline supplementation can induce profound changes in brain function that lead to increased memory capacity and precision in adult offspring. In the present study, the potential benefits of prenatal-choline supplementation were further investigated by using differential reinforcement of low-rate (DRL) schedules to study th...

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Antidepressant-like effects of pregnancy and progesterone in Wistar rats as measured in the differential reinforcement of the low-rate 72 s task

Abstract: Antidepressant-like effects of pregnancy and progesterone were found in Wistar rats as measured in the DRL-72 s task.

Cited by 18 publications

References 28 publications

Inhibition of progesterone metabolism mimics the effect of progesterone withdrawal on forced swim test immobility

Inhibition of progesterone metabolism mimics the effect of progesterone withdrawal on forced swim test immobility

Progesterone attenuates depressive behavior of younger and older adult C57/BL6, wildtype, and progesterone receptor knockout mice

Prenatal choline supplementation alters the timing, emotion, and memory performance (TEMP) of adult male and female rats as indexed by differential reinforcement of low-rate schedule behavior

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