Blandina Bernal-Morales

Allopregnanolone reduces immobility in the forced swimming test and increases the firing rate of lateral septal neurons through actions on the GABAA receptor in the rat

Since allopregnanolone reduces the total time of immobility in rats submitted to the forced swimming test, we decided to explore whether this neuroactive steroid shares other antidepressant-like actions, such as increasing the neuronal firing rate in the lateral septal nucleus (LSN). In order to discard the influence of the oestrous cycle on immobility and on the firing rate of LSN neurons, all Wistar rats used in the study underwent ovariectomy before treatments. A group of rats received different doses of allopregnanolone (0.5, 1.0, 2.0 and 3.0mg/kg, i.p.) 1 hour before being forced to swim in order to identify the minimum effective dose diminishing immobility. None of the tested doses of allopregnanolone produced significant changes in motor activity in the open-field test. The minimum dose of allopregnanolone producing a significant reduction in the total time of immobility (p<0.05) against the vehicle was 1.0mg/kg, while 2.0mg/kg and above also increased the latency to the first period of immobility (p<0.05). The minimum effective dose of allopregnanolone reducing immobility in the forced swimming test (1.0mg/kg) significantly (p <0.05) produced a higher (twofold) neuronal firing rate in LSN neurons, but did not produce any change in septofimbrial nucleus neurons, which fired at a rate similar to that of vehicle-treated rats. The pretreatment with the non-competitive GABAA receptor antagonist, picrotoxin (1.0mg/kg), blocked the aforementioned actions of allopregnanolone on both immobility and LSN firing rate. In conclusion, allopregnanolone produces an antidepressant-like effect in the forced swimming test, associated with an increase in the LSN neuronal firing rate, seemingly mediated by the GABAA receptor.

Amniotic fluid elicits appetitive responses in human newborns: Fatty acids and appetitive responses

In humans, maternal cues guide newborns to the maternal breast, and transitional cues may be present in maternal-fetal fluids. The aim of the present study was to determine the consistent presence of sensorial cues in three maternal-fetal fluids--amniotic fluid, colostrum, and milk--and test the ability of these cues to produce appetitive responses in newborns. In the analytical study, gas chromatography-mass spectrometry (GC-MS) detected eight fatty acids consistently present in the amniotic fluid, colostrum, and milk from 12 healthy volunteers, but we do not find a mammalian pheromone, identified in another mammalian species (rabbits), in another 30 volunteers. In the behavioral study, we explored the ability of amniotic fluid or its fatty acids to produce appetitive responses in 19 human newborns <24u2009hr after birth. Exposure to swabs impregnated with amniotic fluid or an artificial fatty acid mixture produced a longer duration of facial reactions that suggested appetitive (sucking) movements compared with respective vehicles (i.e., propylene glycol or centrifuged amniotic fluid with a low fatty acid content verified by GC-MS). We conclude that the fatty acids contained in amniotic fluid may constitute a transitional sensorial cue that guides newborns to the maternal breast.

Acute restraint stress produces behavioral despair in weanling rats in the forced swim test

Stressful experiences in the rat during early life increase the vulnerability to later signs of behavioral despair in adulthood, reflected in increased immobility in the forced swim test (FST). However, the possible immediate effects of stress in weanling rats have only been partially described. The present study tested whether a single session of mild restraint stress modifies immobility in the FST in 21-day-old Wistar rats. After evaluating any possible changes in locomotion using the open field test (OFT), the latency and total duration of immobility were assessed in a single FST session. Regardless of gender, mild restraint stress significantly reduced crossings in the OFT, shortened the latency to the first period of immobility, and increased immobility in the FST compared with a control group devoid of stress. We conclude that a single mild physical stress session, as early as postnatal day 21, produces signs of behavioral despair.

Phytoestrogens as Potential Therapeutic Agents for the Treatment of Anxiety and Affective Disorders

Abstract Phytoestrogens are natural chemical compounds that are contained in fruits, vegetables, legumes, whole grains, and especially flaxseed, clover, and soy products. They can generally be classified as isoflavones, flavones, lignans, coumestans, and stilbenes. These chemical compounds produce physiological actions that are similar to natural estrogens, such as 17β-estradiol. The phytoestrogens genistein and daidzein, among others, exert the most potent estrogenic activity, acting at estrogen receptor-β. Clinical trials suggest that a phytoestrogen-rich diet or administration of specific doses of phytoestrogens can protect women against age-related diseases, including certain types of cancers, postmenopausal symptoms, anxiety, and affective disorders. However, at the preclinical level, controversy exists with regard to the effects of phytoestrogen on anxiety and mood swings. Rats that are fed a phytoestrogen-rich diet exhibit a reduction of anxiety-like behavior, whereas rats that are fed a phytoestrogen-low diet exhibit an increase in anxiety-like behavior. Low concentrations of phytoestrogens appear to inhibit aromatase and block the biotransformation from testosterone to 17β-estradiol, whereas high concentrations of phytoestrogens produce estrogen-like effects, which may partially explain the differential effects on anxiety-like behavior. Clinical and preclinical studies have shown that phytoestrogens also produce antidepressant-like effects in some subjects, especially women and female rats with the long-term absence of ovarian hormones, such as after natural or surgical menopause. These findings support the therapeutic use of phytoestrogens to ameliorate anxiety and depressive symptoms, but additional studies are necessary to identify possible side effects and interactions with other drugs. Phytoestrogens exert their effects through multiple mechanisms of action, including the activation of estrogen receptor-β, the inhibition of tyrosine kinase and other enzymes, and antioxidant activity, among others. This chapter focuses on preclinical and clinical studies that have evaluated the potential therapeutic effects of phytoestrogens in the management of anxiety and depressive symptoms and the neurobiological substrates of their pharmacological actions.

P03-109 - Involvement of the lateral septal nucleus and GABAa receptors in the antidepressant-like effects of allopregnanolone in wistar rats

Introduction Pharmacological and non-pharmacological antidepressant therapies increase the firing rate of lateral septal nucleus neurons (a brain structure involved in mood state regulation) and reduce immobility in the forced swim test (FST), whereas the neurosteroid allopregnanolone appears to produce antidepressant-like effects through actions at GABAA receptors. Objective To explore the participation of the lateral septal nucleus and GABAA receptors in the antidepressant-like effects of allopregnanolone in Wistar rats. Methods First, the minimally effective dose of allopregnanolone that produces antidepressant-like effects in the FST was determined. Second, the effect of this minimally effective dose in the FST was evaluated on the firing rate of lateral septal neurons. Third, the antidepressant-like effects of microinjection of allopregnanolone (1.0xa0μg/rat) into the lateral septal nucleus was evaluated in the FST. Fourth, we explored whether the effects of allopregnanolone on the lateral septal neuron firing rate and FST are blocked by picrotoxin or bicuculline, two GABAA receptor antagonists. Results The minimally effective dose of allopregnanolone with antidepressant-like effects in the FST was 1.0xa0mg/kg (i.p.) and significantly increased the firing rate of lateral septal neurons. Microinjection of allopregnanolone into the lateral septal nucleus produced antidepressant-like effects in the FST. Pretreatment with picrotoxin and bicuculline blocked the increase in lateral septal neuron firing rate and the antidepressant-like effects of allopregnanolone in the FST. Conclusion The lateral septal nucleus participates in the antidepressant-like effects of allopregnanolone through actions on GABAA receptors in Wistar rats.

P03-406 - Repeated prenatal stress sessions produce changes in exploration and despair detectable at weanling in wistar rats

Introduction During gestation and maternal behavior, some physiological events can protect the dam and offspring, but explanations for such phenomena are partially unknown. The effects of stress during prenatal development and infancy can be studied in controlled laboratory conditions. Objective To determine the pre- and postnatal effects of stress on coping strategies in weanling rats subjected to the open field and forced swim tests after their dams are subjected to stress during gestation. Method Rats aged 21 postnatal days (PND) were assigned to either a Control group (nxa0=xa036; offspring from intact dams during gestation) or a Prenatal stress group (nxa0=xa036; offspring from dams forced to swim during 5xa0min sessions on gestational days 1, 7, 14, and 19). Both groups were tested in the open field to evaluate locomotor activity and rearing. In another experiment, PND21 intact rats assigned to a Control group (nxa0=xa026) or Postnatal stress group (nxa0=xa035) were subjected to restraint stress for 6 min prior to the tests and were later evaluated in the forced swim test. Results Locomotor activity (pxa0 Conclusion Stress exposure during gestation produces detectable changes during weanling, consisting of reduced exploratory activity and susceptibility to despair.