GABAergic drugs alter hypothalamic serotonin release and lordosis in estrogen-primed rats

The effects of muscimol, a GABA(A) agonist, and phaclofen, a GABA(B) antagonist, on serotonin (5HT) release in the mediobasal hypothalamus and lordosis behavior were studied in freely moving rats using in vivo microdialysis. Two days after implantation of bilateral guide cannulae directed towards the ventromedial nucleus of the hypothalamus (VMH), ovariectomized rats were primed with estradiol (E(2)). The rats were implanted with microdialysis probes 24 h later. Following a pretest for lordosis, perfusate 5HT was measured at 20-min intervals until the baseline was stable. The rats were treated with 10, 30 or 100 microM muscimol or 30 and 100 microM phaclofen in artificial CSF delivered via reverse dialysis for 40 min. Control animals were continuously perfused with artificial CSF. Behavior was tested 20, 60 and 180 min after introduction of the drug. Decreased hypothalamic 5HT (40-60% of baseline) and marked facilitation of lordosis were present 20 min after administration of either drug. The effects of 10 and 30 microM muscimol and 30 microM phaclofen on both 5HT and lordosis were reversed after 180 min. Reversal of the behavioral and neurochemical effects were not evident in either the 100 microM muscimol or 100 microM phaclofen groups at the time-points tested. Proceptive responses were observed in phaclofen-treated rats but not in rats treated with muscimol. Levels of hypothalamic 5HT and lordosis quotients in control rats did not significantly differ from initial values. These results suggest that GABAergic effects on lordosis may be mediated through an interaction with 5HT in the mediobasal hypothalamus.     

Alpha 1-noradrenergic regulation of hypothalamic progestin receptors and guinea pig lordosis behavior

Experiments were conducted to determine whether alpha 1- or alpha 2-receptors mediate noradrenergic (NA) regulation of guinea pig lordosis behavior and hypothalamic progestin receptors. When infused into a lateral cerebroventricle at a dose that inhibits lordosis and that decreases the concentration of estradiol-inducible hypothalamic progestin receptors, phenoxybenzamine decreased binding of the alpha 1-ligand [3H]WB4101 but not the alpha 2-ligand [3H]clonidine to brain membranes. Thus, under the conditions used, phenoxybenzamine appears to block alpha 1-receptors with little or no effect on alpha 2-receptors. Experiments with the selective alpha 1-antagonist prazosin also indicated alpha 1-receptor regulation of lordosis and hypothalamic progestin receptors. Prazosin inhibited lordosis induced by estradiol benzoate (EB) plus progesterone and by EB + clonidine and decreased the concentration of cytoplasmic progestin receptors in hypothalamus (but not in preoptic area or frontal cortex) of EB-primed females. The inhibition of lordosis is apparently not due to some unknown side effect of prazosin because pretreatment with a high dose of clonidine attenuated the inhibition. The possibility that a causal relationship exists between effects of alpha 1-NA transmission on hypothalamic progestin receptors and lordosis was discussed. Also, because effects of NA transmission on hypothalamic progestin receptors are dependent on prior treatment with EB, it was suggested that NA transmission might influence estradiol action in addition to progestin action in hypothalamic cells.     

Progestin receptors in the ventromedial nucleus of the hypothalamus and arcuate nucleus-median eminence are decreased by idazoxan

Steroid-dependent lordosis behavior in ovariectomized (OVX) guinea pigs is attenuated by alpha 1- and/or alpha 2-noradrenergic (NE) receptor antagonists. Correlated with the decrease in lordosis after alpha 1-NE receptor blockade by prazosin is a decrease in 'cytosol' progestin receptors in the ventromedial hypothalamic nucleus (VMN). We examined whether a presumed alpha 2-NE receptor blocker (idazoxan, IDA) also affects progestin receptors. A decrease in 'cytosol' progestin receptors was found after IDA treatment of OVX, estrogen-treated guinea pigs in the VMN and the arcuate nucleus-median eminence (ARC-ME). Apparently, either prazosin or IDA can inhibit lordosis behavior and decrease 'cytosol' progestin receptors in the VMN. In contrast, idazoxan but not prazosin, decrease 'cytosol' progestin receptors in the ARC-ME.     

Tamoxifen and mifepriston modulate nicotine induced conditioned place preference in female rats

An increasing number of studies suggest that nicotine/tobacco addiction is modulated by ovarian hormones. The levels of estrogen and progesterone appear to be important in the success of quit attempts and smoking cessation. In women smokers with the diagnosis or risk of breast cancer, the estrogen receptor modulator tamoxifen (TAM) is widely used, and even though the detrimental health effects of smoking are known, this vulnerable group has difficulty quitting and continues to smoke. The current study tested the effect of the estrogen receptor modulator TAM and the progesterone receptor antagonist mifepriston (RU486) on nicotine-induced conditioned place preference (CPP) in adult female rats. A three chambered CPP apparatus was used and nicotine was paired with the initially non-preferred chamber. Rats received nicotine or saline and hormone receptor modulators (vehicle, TAM, RU486) in a 2 × 3 experimental design. We have previously shown that nicotine induces CPP in male Sprague-Dawley rats but not in females. Our results show that while nicotine alone does not induce CPP in female rats, rats treated with TAM exhibit nicotine-induced CPP. Although RU486 has an aversive effect when applied alone, this is ameliorated by nicotine. These results confirm the role of ovarian hormone receptors in nicotine-induced CPP and may have clinical implications for developing more efficient smoking cessation approaches in women smokers.     

Effects of septal lesions and testosterone on lordosis behavior and luteinizing hormone release in female rats

The increased behavioral sensitivity to estrogen following a septal lesion in female rats has previously been found to be blocked by chronic treatment with testosterone propionate (TP) following the lesion. The effects of this chronic treatment on the ability of progesterone (P) to facilitate the secretion of luteinizing hormone (LH) in the spayed septal lesioned rat primed with estradiol benzoate (EB) was tested in the present study. EB was injected and followed 72 hr later with an injection of P. Blood samples for measurement of plasma LH were taken at 1700 hr, 29 and 53 hr after EB and 5 hr after P injection. Although there was no effect of the lesion, TP treatment significantly inhibited LH values after P administration. In a second experiment, spayed septal lesioned or sham operated rats were given either 0.0, 0.5 or 2.0 μg EB followed by 0.5 mg P just 24 hr later. The display of lordosis behavior, tested 4–6 hr after P injection, was significantly greater in septal lesioned than in sham operated rats following priming injections of 0.5 or 2.0 μ EB. This indicates that septal destruction significantly shortened the duration required for estrogen to prepare neural mechanisms for the effect of progesterone on lordosis behavior. Following a similar steroid regime, no differences were found between lesioned and sham operated rats in plasma LH levels in blood samples taken 5 hr after EB or 5 and 29 hr after P injection.     

Activation of protein kinase C in the hypothalamic ventromedial nucleus or the midbrain central gray facilitates lordosis

Many neurotransmitters and neuropeptides can act through the hypothalamic ventromedial nucleus (VMN) or midbrain central gray (MCG) to facilitate lordosis. Since these lordosis-facilitating agents can also stimulate the phosphoinositide (PI) second-messenger pathway, it was hypothesized that direct activation of this pathway can also potentiate the behavior. To evaluate this possibility, a phorbol ester, TPA (12-O-tetradecanoyl phorbol 13-acetate), was used to activate a key enzyme, protein kinase C (PKC), of the PI pathway in ovariectomized (OVX) rats either primed or not primed with estrogen. These female rats were paired with males for mating tests before and after an intracerebral infusion of TPA, and both the lordosis quotient (LQ) and the lordosis strength (LS) were measured. Bilateral infusion of TPA (5 μg/0.5 μl or 0.2 μg/0.2 μl, but not 0.1 μg/0.2 μl/side) into the VMN or MCG of estrogen-primed subjects facilitated both LQ and LS in 30 min, peaked at 60–90 min, and the facilitation lasted for more than 180 min. This facilitatory effect of TPA was: (1) not observed in OVX rats not primed with estrogen; (2) not observed if the infused TPA did not reach both sides of the VMN or MCG; (3) not mimicked by 4-phorbol 12,13-didecanoate, which does not activate PKC; (4) blocked by PKC inhibitors (H7 10 mM or staurosporine 1 μM, 0.2 μl/ side), which by themeselves did not facilitate lordosis; and (5) was not affected by pretreatment of the progestin antagonist RU486. These observations indicate that TPA facilitates lordosis in a dose-dependent fashion by activating, and not by depleting, PKC in the VMN or MCG, and that the TPA effect requires estrogen priming but not the activation of progestin receptors. Thus, the PI pathway or the activation of PKC may be a common mediator for lordosis facilitation in these two brain regions; and the requirement of estrogen priming further raises the possibility that this second-messenger system or its substrates in the VMN and MCG are modulated by estrogen.     

Alterations by estrogen and hypothyroidism in the effects of septal lesions on lordosis behavior of male rats

Earlier experiments indicated that chronic exposure to estradiol benzoate (EB) following septal lesions can increase the subsequent levels of female sexual behavior in male rats tested several months later following priming doses of EB. However, the present study demonstrates that a single injection of a large dose of EB (50 μg) two days after septal destruction did not modify subsequent responsiveness to EB priming in male rats relative to sham operated controls. Yet male rats given 10 daily injections of 5.0 μg EB/day immediately following a septal lesion were more responsive to EB than oil treated controls when tested later for lordosis behavior. Therefore, the capacity for EB to alter the behavioral effects of septal lesions on lordosis behavior in male rats is related to both chronic administration and a period of susceptibility to some action of EB during the immediate post-lesion period. In two additional experiments, chronic hypothyroidism induced by propylthiouracil or thyroidectomy was also found to modify the effects of septal lesions on female sexual behavior of male rats. These latter results indicate that EB is not unique in its capacity to alter the behavioral effects of septal lesions in male rats, and are consistent with the view that both EB and hypothyroidism may interact with some dynamic process associated with recovery from brain lesions.     

α1-Noradrenergic regulation of hypothalamic progestin receptors and guinea pig lordosis behavior

Experiments were conducted to determine whetherα₁- orα₂-receptors mediate noradrenergic (NA) regulation of guinea pig lordosis behavior and hypothalamic progestin receptors. When infused into a lateral cerebroventricle at a dose that inhibits lordosis and that decreases the concentration of estradiol-inducible hypothalamic progestin receptors, phenoxybenzamine decreased binding of theα₁-ligand [³H]WB4101 but not theα₂-ligand [³H]clonidine to brain membranes. Thus, under the conditions used, phenoxybenzamine appears to blockα₁-receptors with little or no effect onα₂-receptors.Experiments with the selectiveα₁-antagonist prazosin also indicatedα₁-receptor reguilation of lordosis and hypothalamic progestin receptors. Prazosin inhibited lordosis induced by estradiol benzoate (EB) plus progesterone and by EB + clonidine and decreased the concentration of cytoplamic progrestin receptors in hypothalamus (but not in area or frontal cortex) of EB-primed females. The inhibition of lordosis is apparently not due to some unknown side effect of prazosin because pretreatment with a high dose of clonidine attenuated the inhibition.The possibility that a causal relationship exists between effects ofα₁-NA transmission on hypothalamic progestin receptors and lordosis was discussed. Also, because effects of NA transmission on hypothalamic progestin receptors are dependent on prior treatment with EB, it was suggested that NA transmission might influence estradiol action in addition to progestin action in hypothalamic cells.     

Expression of intracellular progesterone receptors in rat brain during different reproductive states, and involvement in maternal behavior

Progesterone is one of a complex of hormones which influences the occurrence of maternal behavior in rats. The present study provides information on progesterone's mechanism and possible neural site(s) of action with respect to maternal responsiveness. Progesterone can exert cellular effects by acting on membrane receptors or by acting on intracellular receptors. In the first experiment we show that RU 486 can antagonize progesterone's inhibitory effect on maternal behavior. Since RU 486 acts as an antagonist to progesterone's action at its intracellular receptor, these results support the involvement of that receptor in maternal behavior control. The second experiment employs immunocytochemical techniques to detect the number of cells in various forebrain regions which contain intracellular progesterone receptors during different reproductive states. The number of cells which contained progesterone receptors was higher toward the end of pregnancy (progesterone is presumably exerting its effects on maternal behavior at this time) when compared to either early pregnancy or lactation in the following forebrain regions: anteroventral periventricular nucleus of the preoptic area; medial preoptic area; ventral part of the bed nucleus of stria terminalis; ventrolateral division of the ventromedial nucleus; arcuate nucleus; anterior paraventricular nucleus of the hypothalamus; and medial amygdala. The possible involvement of these regions as a site or sites where progesterone might exert its effects on maternal behavior is discussed.     

Effects of estrogen on dopamine turnover, glutamic acid decarboxylase activity and lordosis behavior in septal lesioned female rats

Estradiol benzoate (EB) treatment (2.0 μg/day × 3) of septal lesioned adult female rats produces a marked increase in lordosis behavior over similarly treated sham operated animals. In these animals endogenous dopamine (DA) and norepinephrine (NE) levels were measured and turnover rates were estimated following tyrosine hydroxylase inhibition with α-methyltyrosine, in both EB and oil (0.05 ml × 3 days) treated groups. No consistent pattern of change in the level or rate of turnover of NE was noted for any of the treatment groups. No differences in either the level or turnover of DA were seen in the oil treated septal lesioned group, relative both to EB and oil treated sham operated groups. However, in the amygdala, corpus striatum and nucleus accumbens septi of the septal lesioned animals primed with EB there was both a reduction in endogenous levels (20–50%) and a decrease in synthesis rates (30–70%) of DA relative to both EB and oil treated sham operated groups and the oil treated septal lesioned group. The EB treated septal lesioned animals showed a significant negative correlation between DA levels in the corpus striatum and the level of lordosis behavior (r = −.850), supporting the concept of a possible inhibitory role for DA on female sexual receptivity. Glutamic acid decarboxylase (GAD; the rate limiting enzyme in the synthesis of γ-aminobutyric acid (GABA)) activity was measured in the substantia nigra and ventral tegmental region from the same animals. GAD activity was reduced in both areas in the EB primed sham operated animals, while the EB and oil treated septal lesioned groups remained comparable to the oil treated sham operated animals. Because of the proposed existence of a GABA mediated inhibitory neuronal feedback on DA cell bodies in the midbrain, the reduction in DA turnover in the EB primed septal lesioned female rat and thus the increase in behavioral receptivity could be due in part to the failure of the septal lesioned animal to show a compensatory decrease in GAD activity.     

Lesions of the preoptic area facilitate lordosis behavior in male and female guinea pigs

Male and female guinea pigs received radiofrequency lesions in the medial preoptic area (MPOA). Animals were gonadectomized, treated with estrogen and progesterone, and tested for the occurrence of the lordosis response to manual stimulation. Females with MPOA lesions exhibited enhanced lordosis behavior, shorter latencies to heat, longer duration of heat and longer maximum lordosis duration than sham control females. In males with MPOA lesions, the lordosis response could be elicited by manual stimulation, in contrast to no response in the sham control males. Furthermore, MPOA-lesioned males were insensitive to the inhibitory effects of progesterone on lordosis behavior, while MPOA-lesioned females were as sensitive as sham controls to the inhibitory effects of progesterone. The results suggest that a neural mechanism resides within the MPOA which inhibits the occurrence of lordosis behavior in both male and female guinea pigs and which is not involved in a sexual dimorphism in responsiveness to progesterone.     

Effects of septal lesions and chronic estrogen treatment on dopamine,GABA and lordosis behavior in male rats

GORDON, J. H., D. M. NANCE, C. J. WALLIS AND R. A. GORSKI. Effects of septal lesions and chronic estrogentreatment on dopamine, GABA and lordosis behavior in male rats. BRAIN RES. BULL. 4(1) 85–89, 1979.—Septal lesions (SL) in female rats result in an increased sensitivity to the behavioral effects of acute estradiol benzoate (ACUTE-EB; 2 μg/day × 3) treatment as measured by the lordosis quotient (LQ; number of lordotic responses × 100/number of mounts). Male rats, intact or castrated, do not show this enhanced behavioral response to ACUTE-EB unless they are treated with EB (2 μg/day) for 2–4 weeks immediately following the production of SL. The present study was undertaken to examine possible neurochemical alterations which could account for the enhanced behavioral sensitivity to ACUTE-EB seen in the SL male rat treated chronically with EB during the postlesion period (SL-EB). Three groups, normal males, SL-EB and SL males chronically treated with oil (SL-oil), were subdivided and treated with ACUTE-EB or oil and decapitated. The brains were removed, frozen and stored at ?50°C prior to dissection and assay. Tyrosine hydroxylase (TH) activity was assayed in the dopamine (DA) rich areas of the forebrain (striatum, STR; nucleus accumbens septi, ACB; and olfactory tubercle). The TH activity was significantly suppressed in both the STR and ACB of the SL-EB males treated with ACUTE-EB. The glutamic acid decarboxylase (GAD) activity in both the substantia nigra and ventral tegmentum was significantly increased in the SL-EB males given ACUTE-EB relative to that of all other groups. In summary, SL-EB males given ACUTE-EB show (1) an enhanced LQ, (2) decreased TH activity in the region of DA terminals, and (3) increased GAD activity in the region of DA cell bodies. The increase in GAD activity is suggested to be a result of an altered neuronal feedback because of plastic changes that occur during chronic EB treatment following production of SL. This probable increase in inhibitory tone in the region of the DA cell bodies may explain the observation that the SL-EB male exhibits decreased DA turnover following ACUTE-EB treatment. Moreover, since DA may be inhibitory to the display of lordosis behavior, the SL-EB males may show an enhanced LQ, at least partially, because of this reduction in DA activity.     

Abbreviation of the period of sexual behavior in female guinea pigs by the progesterone antagonist RU 486

In previous studies we have tested the hypothesis that the termination of the period of sexual behavior in female guinea pigs results from the loss of progestin receptors from hypothalamic cell nuclei. We have shown that hormonal manipulations that delay heat termination also delay loss of hypothalamic nuclear progestin receptors. In order to determine if accelerated nuclear receptor loss results in abbreviation of the period of sexual behavior, we tested the effect of 17 beta-hydroxy-11 beta-(4-dimethylaminophenyl)-17 alpha-(1-propyl)-estra-4,9-diene-3-one (RU 486), a progesterone antagonist, on heat termination. Ovariectomized guinea pigs were treated with estradiol benzoate. Forty hours later, they received progesterone followed 4 h later by injection of RU 486 or vehicle. RU 486 injected 4 h after progesterone caused heat abbreviation. We have found that RU 486 administration to estradiol-treated guinea pigs causes accumulation of progestin receptors in cell nuclear extract. Because this accumulation can be detected only when assay conditions are used that promote exchange of RU 486 progestin receptor complexes (15 degrees C incubation rather than 0 degree C); our routine assay conditions (at 0 degree C) can be used to measure primarily receptors that are occupied by progesterone. In order to confirm that RU 486 decreased progesterone-occupied nuclear progestin receptor levels when injected 4 h after progesterone, animals treated as in the behavioral experiment were killed 6 or 10 h after progesterone injection (2 or 6 h after RU 486), and nuclear progestin receptor levels were measured. RU 486 treatment resulted in lowered nuclear concentrations of hypothalamic progestin receptors at both times. These results support our hypothesis that the termination of the period of sexual receptivity in female guinea pigs is the result of loss of progestin receptors from hypothalamic cell nuclei.     

Chronic blockade of glucocorticoid receptors by RU486 enhances lipopolysaccharide-induced depressive-like behaviour and cytokine production in rats

Although accumulating evidence supports a role for cytokines in the pathophysiology of depression, the cytokine hypothesis of depression is debatable. It has been suggested that neuroendocrine and immune systems acting in concert may have roles in the development and the maintenance of the disease. Glucocorticoid receptor (GR) is the key element which exerts both anti-inflammatory and cytokine-inhibiting effects. Whether functional changes of GR are involved in the pathophysiology of cytokine-induced depression remains elusive. In the present study, the effects of both acute and chronic GR blockade on depressive-like behaviour and cytokine production induced by lipopolysaccharides (LPS), cytokine inducer, were investigated in rats. Acute or chronic blockade of GR was achieved by a single administration or repeated administrations, respectively, of the GR antagonist RU486 (RU). Behavioural measurements, including saccharin preference, locomotor activity, and immobility time, were assessed. The serum levels of proinflammatory cytokines (TNFα, IL-1β, and IFNγ) were determined by ELISA. The results showed that LPS induced significant but transient depressive-like behaviour. Repeated, but not single, administration of RU significantly enhanced and prolonged LPS-induced depressive-like behaviour and an increase in the serum production of TNFα and IFNγ. These results indicate that the effective blockade of GR enhanced the depressive-like behaviour induced by cytokines. Findings from this study suggest that GR dysfunction may be an important contributing factor to the development of cytokine-related depression. These findings add to the growing evidence of mechanisms by which cytokines influence depression.     

Effects of hypothalamic and preoptic lesions on reproductive behavior in male rats

Adult male rats, which were selected on the basis of showing complete patterns of male copulatory behavior on two prior tests, were castrated six weeks prior to brain surgery. Animals were divided into three groups and given small bilateral lesions in the dorsomedial preoptic area (POA), ventromedial hypothalamus (VMH), or sham operations. Starting 10 days postsurgery, all animals were injected with estrogen alone and estrogen plus progesterone, and tested twice for lordosis behavior. Ten days following the female behavior tests, animals were injected daily with testosterone propionate for 13 days and tested for masculine sexual behavior on injection days 5, 9 and 13. Low levels of lordotic behavior were observed for POA and VMH animals on both tests for female sex behavior and were comparable to sham operated animals. However, in terms of all dependent measures of male copulatory behavior, animals with VMH lesions showed significantly higher levels of male sex behavior with shorter latencies than sham animals across all three behavior tests. In contrast, POA lesioned rats showed little or no male sex behavior on any test and were significantly inferior to sham operated animals. Thus, the POA and VMH appear to exert excitatory and inhibitory control, respectively, over male copulatory behavior in male rats.     

Progesterone attenuates the effect of the 5-HT1A receptor agonist, 8-OH-DPAT,and of mild restraint on lordosis behavior

Ovariectomized, hormone-primed rats were used to test the hypothesis that progesterone treatment attenuated the effects of the 5-HT(1A) receptor agonist, (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), on female rat lordosis behavior. Based upon prior evidence that prepriming with estradiol benzoate (EB) reduced the ability of 8-OH-DPAT to inhibit lordosis behavior, rats were preprimed with 10 microg EB 7 days before a second priming with 10 microg EB followed 48 h later with 500 microg progesterone or vehicle. Independent of the presence of progesterone, prepriming with EB attenuated the lordosis-inhibiting effects of systemic treatment with 8-OH-DPAT. However, progesterone also reduced the effects of 8-OH-DPAT and this effect was also seen in females primed only once with EB. In contrast, progesterone was relatively ineffective in attenuating the effects of bilateral infusion with 8-OH-DPAT into the ventromedial nucleus of the hypothalamus (VMN). The failure of progesterone to substantially reduce the effects of VMN infusion with 8-OH-DPAT contrasts with prior studies in which estrogen's protective action against the drug did include the VMN. Thus, while both estrogen and progesterone reduce the lordosis-inhibiting effect of 8-OH-DPAT, the mechanisms responsible for the effects of the two gonadal hormones may be different. Priming with progesterone also prevented the effects of 5 min of restraint. When rats were hormonally primed with EB and oil, rats showed a transient, but significant, decline in lordosis behavior 5 and 10 min after restraint. Rats primed with EB and progesterone were unaffected by the restraint. These results are discussed in terms of their implications for the role of progesterone in altering the 5-HT(1A) receptor modulation of lordosis behavior.     

Differential effects of IL-1ra on sickness behavior and weight loss induced by IL-1 in rats

Peripheral and central injections of recombinant human interleukin-1β (IL-1β) have been shown to decrease social exploration and to induce body weight loss in rats. To characterize the receptor mechanisms of these effects, we used as a tool a specific antagonist of the receptors of IL-1, IL-1ra. Intraperitoneal (i.p.) administration of IL-1ra (8 mg/kg) blocked the effect of i.p. injection of IL-1β (4 μg/rat) on social behaviour but not on body weight. Central administration of IL-1ra (60 μg/rat, i.c.v.) abrogated the effects of centrally administered IL-1β (30 ngn/rat, i.c.v.) on both social behaviour and body weight. Central injection of IL-1ra (4 μg/rat, i.c.v.) also attenuated the effects of i.p. administered IL-1β (4 μg/rat) on social behaviour but not on body weight. These results suggest that the effects of IL-1β on social behavior are mediated centrally and that its effect on the loss of body weight involves different receptor mechanisms.     

Prolactin and glucocorticoid receptors in the prefrontal cortex are associated with anxiety-like behavior in prenatally stressed adolescent offspring rats

Prenatal stress (PS) causes anxiety in mothers and their offspring and chewing is a commonly observed behavior during maternal stress. Prolactin (PRL) is an anti-anxiety factor that suppresses the hypothalamic–pituitary–adrenal axis. Here, we studied the roles of PRL, corticosterone (CORT), and their receptors in PS-induced anxiety-like behavior in dams and their offspring. We further investigated whether chewing during maternal stress could prevent PS-induced harmful consequences. Pregnant rats were randomly divided into PS, PS + chewing, and control groups. Anxiety-like behaviors of dams and their adolescent offspring were assessed using the open field test and elevated plus maze. Serum levels of PRL and CORT were measured by ELISA. Expression of mRNA and protein of PRLR and glucocorticoid receptor (GR) in the prefrontal cortex (PFC) were evaluated by qRT-PCR and western blotting, respectively. Compared to the control rats, dams and their female offspring, but not male offspring, in the PS group showed increased anxiety-like behaviors. The PS-affected rats had a lower serum PRL level and increased PRLR expression in the PFC. In contrast, these rats had a higher serum CORT level and decreased GR expression in the PFC. Chewing ameliorated anxiety-like behaviors and counteracted stress-induced changes in serum PRL and CORT, as well as the expression of their receptors in the PFC. Conclusion: PS-induced anxiety-like behavior is associated with changes in the serum levels of PRL and CORT and expression of their receptors in the PFC. Moreover, chewing blunts the hormonal and receptor changes and may serve as an effective stress-coping method for preventing PS-induced anxiety-like behavior.     

Early postnatal diazepam exposure facilitates maternal behavior in virgin female rats

Virgin female rats do not display maternal behavior if they are not exposed to the pups during several days. This exposure is called induction. In this work we have studied the effects of early postnatal (PO-P16) diazepam (DZ) administration (1 and 2.5 mg/kg, SC) on the display of maternal behavior of virgin female rats when adults. Although we did not find statistically significant differences between PO-1318 DZ treated and control females with respect to the latency of retrieval, PO-1318 DZ administration resulted in a statistically significant increase of the percentage of female rats that became maternal, showing retrieval behavior. This early postnatal treatment with DZ also increased other variables that are currently measured in maternal behavior tests, such as: time of physical contacts, grooming, crouching, and nest building quality. No statistically significant differences were found in the body weight of treated versus control animals during development, nor during adulthood. Our results provide further evidence that the GABA_A-BDZ-Cl⁻ receptor complex is implicated in the development of maternal behavior in female rats.