Experimental anxiety in the black and white model in cycling, pregnant and lactating rats

Zuluaga, María José; Agrati, Daniella; Pereira, Mariana; Uriarte, Natalia; Fernández‐Guasti, Alonso; Ferreira, Annabel

doi:10.1016/j.physbeh.2004.12.004

Cited by 64 publications

(42 citation statements)

References 78 publications

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“…Proestrous, compared to diestrous, rats had higher levels of E 2 and progestins in serum, midbrain, hippocampus, diencephalon, and cortex, which were commensurate with previous reports that examined endocrine parameters across the estrous cycle [33,50]. In the present study, proestrous rats engaged in more exploratory, anxiolytic, social, and sexual behavior than did diestrous rats, which is consistent with prior reports that separately investigated changes in these behavioral processes across the estrous cycle [14,16,51,52]. The present experiment uniquely demonstrates contemporaneous changes in exploratory, anxiolytic, and social behaviors with reproductive behaviors.…”

Section: Discussionsupporting

confidence: 91%

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Infusions of 3α,5α-THP to the VTA enhance exploratory, anti-anxiety, social, and sexual behavior and increase levels of 3α,5α-THP in midbrain, hippocampus, diencephalon, and cortex of female rats

Frye

Rhodes

2008

Behavioural Brain Research

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Abstract17β-Estradiol (E 2 ) and progesterone (P 4 ) influence the onset and duration of sexual behavior and are also associated with changes in behaviors that may contribute to mating, such as exploration, anxiety, and social behaviors (socio-sexual behaviors). In the midbrain ventral tegmental area (VTA), the P 4 metabolite, 5α-pregnan-3α-ol-20-one (3α,5α-THP), modulates lordosis of E 2 -primed rodents; 3α,5α-THP can also influence anxiety and social behaviors. To examine if 3α,5α-THP in the VTA mediates socio-sexual behaviors, we infused 3α,5α-THP to the VTA of diestrous and proestrous rats. As expected, proestrous, compared to diestrous, rats showed more exploratory (open field), anxiolytic (elevated plus maze), pro-social (partner preference, social interaction), and sexual (paced mating) behavior and had increased E 2 , P 4 , dihydroprogesterone (DHP), and 3α,5α-THP in serum, midbrain, hippocampus, diencephalon, and cortex. Infusions of 3α,5α-THP to the VTA, but not control sites, such as the substantia nigra (SN) or central grey (CG), of diestrous rats produced behavioral and endocrine effects akin to that of proestrous rats and increased DHP and 3α,5α-THP levels in midbrain, hippocampus, and diencephalon. Levels of DHP and 3α,5α-THP, but neither E 2 nor P 4 concentrations, in midbrain, hippocampus, diencephalon, and/or cortex were positively correlated with socio-sexual behaviors. Thus, 3α,5α-THP infusions to the VTA, but not SN or CG, can enhance socio-sexual behaviors and increase levels in midbrain, hippocampus, and diencephalon.

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Section: Discussionsupporting

confidence: 91%

“…Exploration, anti-anxiety, and pro-social behaviors of female rodents are increased during behavioral estrus, when E 2 and 3α,5α-THP levels are high, relative to other phases of the estrous cycle [13][14][15][16][17]. Increasing levels of 3α,5α-THP in brain enhances exploratory, anti-anxiety, and social behaviors.…”

Section: Introductionmentioning

confidence: 99%

Infusions of 3α,5α-THP to the VTA enhance exploratory, anti-anxiety, social, and sexual behavior and increase levels of 3α,5α-THP in midbrain, hippocampus, diencephalon, and cortex of female rats

Frye

Rhodes

2008

Behavioural Brain Research

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“…These effects of pregnancy on the subunit composition and function of GABA A -Rs were inhibited by treatment with finasteride, suggesting that they are mediated by the associated changes in the brain levels of 3␣,5␣-THP and other neuroactive steroids during late pregnancy . Such an increase in GABAergic tonic at day 19 of pregnancy may be important to further reduce the excitability and anxiety level usually associated with the end of pregnancy and immediately preceding delivery (Zuluaga et al, 2005;de Brito Faturi et al, 2006;Skouteris et al, 2009). The brain levels of steroid hormones increase markedly during pregnancy in rats .…”

Section: Discussionmentioning

confidence: 99%

Changes in Expression and Function of Extrasynaptic GABA_AReceptors in the Rat Hippocampus during Pregnancy and after Delivery

Sanna¹,

Mostallino²,

Murru³

et al. 2009

J. Neurosci.

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Pregnancy is associated with changes in mood and anxiety level as well as with marked hormonal fluctuations. Increases in the brain concentrations of neuroactive steroids during pregnancy in rats are accompanied by changes in expression of subunits of the GABA type A receptor (GABA A -R) in the brain. Granule cells of the dentate gyrus (DGGCs) exhibit two components of inhibitory GABAergic transmission: a phasic component mediated by synaptic GABA A -Rs, and a tonic component mediated by extrasynaptic GABA A -Rs. Recordings of GABAergic currents were obtained from hippocampal slices prepared from rats in estrus, at pregnancy day 15 (P15) or P19, or at 2 d after delivery. Exogenous GABA or 3␣,5␣-THP induced an increase in tonic current in DGGCs that was significantly greater at P19 than in estrus. Neither tonic nor phasic currents were affected by pregnancy in CA1 pyramidal cells. Immunohistochemical analysis revealed a marked increase in the abundance of the ␦ subunit of the GABA A -R and a concomitant decrease in that of the ␥ 2 subunit in the hippocampus at P19. Expression of the ␣ 4 subunit did not change during pregnancy but was increased 2 d after delivery. Treatment of rats from P12 to P18 with the 5␣-reductase inhibitor finasteride prevented the changes in tonic current and in ␦ and ␥ 2 subunit expression normally apparent at P19. These data suggest that the number of extrasynaptic GABA A -Rs is increased in DGGCs during late pregnancy as a consequence of the associated marked fluctuations in the brain levels of neuroactive steroids.

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“…Circulating and umbilical cord levels of THP peak at delivery, but rapidly decline in the postpartum period. In the rodent peak levels of THP are achieved by day 19 of pregnancy and ∼ 70 nM, 2-fold higher than seen across the circadian cycle (Concas et al, 1999;Zuluaga et al, 2005). Thus, pregnancy represents the most significant exposure to THP in terms of duration and concentration.…”

Section: Pregnancymentioning

confidence: 99%

Neurosteroid regulation of GABAA receptors: Focus on the α4 and δ subunits

Smith

Shen

Gong

et al. 2007

Pharmacology & Therapeutics

211

197

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Neurosteroids, such as the progesterone metabolite 3α-OH-5α[β]-pregnan-20-one (THP or [allo] pregnanolone), function as potent positive modulators of the GABA A receptor (GABAR) when acutely administered. However, fluctuations in the circulating levels of this steroid at puberty, across endogenous ovarian cycles, during pregnancy or following chronic stress produce periods of prolonged exposure and withdrawal, where changes in GABAR subunit composition may occur as compensatory responses to sustained levels of inhibition. A number of laboratories have demonstrated that both chronic administration of THP as well as its withdrawal transiently increase expression of the α4 subunit of the GABAR in several areas of the central nervous system (CNS) as well as in in vitro neuronal systems. Receptors containing this subunit are insensitive to benzodiazepine (BDZ) modulation and display faster deactivation kinetics, which studies suggest underlie hyperexcitability states. Similar increases in α4 expression are triggered by withdrawal from other GABA-modulatory compounds, such as ethanol and BDZ, suggesting a common mechanism. Other studies have reported puberty or estrous cycle-associated increases in δ-GABAR, the most sensitive target of these steroids which underlies a tonic inhibitory current. In the studies reported here, the effect of steroids on inhibition, which influence anxiety state and seizure susceptibility, depend not only on the subunit composition of the receptor but also on the direction of Cl -current generated by these target receptors. The effect of neurosteroids on GABAR function thus results in behavioral outcomes relevant for pubertal mood swings, premenstrual dysphoric disorder and catamenial epilepsy, which are due to fluctuations in endogenous steroids.

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Experimental anxiety in the black and white model in cycling, pregnant and lactating rats

Cited by 64 publications

References 78 publications

Infusions of 3α,5α-THP to the VTA enhance exploratory, anti-anxiety, social, and sexual behavior and increase levels of 3α,5α-THP in midbrain, hippocampus, diencephalon, and cortex of female rats

Infusions of 3α,5α-THP to the VTA enhance exploratory, anti-anxiety, social, and sexual behavior and increase levels of 3α,5α-THP in midbrain, hippocampus, diencephalon, and cortex of female rats

Changes in Expression and Function of Extrasynaptic GABA_AReceptors in the Rat Hippocampus during Pregnancy and after Delivery

Neurosteroid regulation of GABAA receptors: Focus on the α4 and δ subunits

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Experimental anxiety in the black and white model in cycling, pregnant and lactating rats

Cited by 64 publications

References 78 publications

Infusions of 3α,5α-THP to the VTA enhance exploratory, anti-anxiety, social, and sexual behavior and increase levels of 3α,5α-THP in midbrain, hippocampus, diencephalon, and cortex of female rats

Infusions of 3α,5α-THP to the VTA enhance exploratory, anti-anxiety, social, and sexual behavior and increase levels of 3α,5α-THP in midbrain, hippocampus, diencephalon, and cortex of female rats

Changes in Expression and Function of Extrasynaptic GABAAReceptors in the Rat Hippocampus during Pregnancy and after Delivery

Neurosteroid regulation of GABAA receptors: Focus on the α4 and δ subunits

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Changes in Expression and Function of Extrasynaptic GABA_AReceptors in the Rat Hippocampus during Pregnancy and after Delivery