Reading and Theory of Mind in Adolescents with Cochlear Implant.

Previous research has shown a possible link between reading comprehension and theory of mind (ToM), but these findings are unclear in adolescents with cochlear implants (CI). In the present study, reading comprehension and ToM were assessed in adolescents with CI and the relation between both skills was also studied. Two sessions were performed on two groups of adolescents aged between 12 and 16 years of age (36 adolescents with CI and 54 participants with typical hearing, TH). They were evaluated by means of a standardized reading battery, a false belief task, and Faux Pas stories. The results indicated that reading and cognitive ToM were more developed in the TH group than in adolescents with CI. However, early-CI and binaural group performance were close to the TH group in narrative and expository comprehension and cognitive ToM. The results also indicated that cognitive ToM and reading comprehension appear to be related in deaf adolescents.

Effects of neonatal allopregnanolone manipulations and early maternal separation on adult alcohol intake and monoamine levels in ventral striatum of male rats.

Changes in endogenous neonatal levels of the neurosteroid allopregnanolone (AlloP) as well as a single 24h period of early maternal separation (EMS) on postnatal day (PND) 9 affect the development of the central nervous system (CNS), causing adolescent/adult alterations including systems and behavioural traits that could be related to vulnerability to drug abuse. In rats, some behavioural alterations caused by EMS can be neutralised by previous administration of AlloP. Thus, the aim of the present work is to analyse if manipulations of neonatal AlloP could increase adult alcohol consumption, and if EMS could change these effects. We administered AlloP or finasteride, a 5α-reductase inhibitor, from PND5 to PND9, followed by 24h of EMS at PND9. At PND70 we measured alcohol consumption using a two-bottle free-choice model (ethanol 10% (v/v)+glucose 3% (w/v), and glucose 3% (w/v)) for 15days. Ventral striatum samples were obtained to determine monoamine levels. Results revealed that neonatal finasteride increased both ethanol and glucose consumption, and AlloP increased alcohol intake compared with neonatal vehicle-injected animals. The differences between neonatal groups in alcohol consumption were not found in EMS animals. In accordance, both finasteride and AlloP animals that did not suffer EMS showed lower levels of dopamine and serotonin in ventral striatum. Taken together, these results reveal that neonatal neurosteroids alterations affect alcohol intake; an effect which can be modified by subsequent EMS. Thus, these data corroborate the importance of the relationship between neonatal neurosteroids and neonatal stress for the correct CNS development.

Neonatal finasteride administration alters hippocampal α4 and δ GABAAR subunits expression and behavioural responses to progesterone in adult rats.

Allopregnanolone is a neurosteroid that has been reported to fluctuate during early developmental stages. Previous experiments reported the importance of neonatal endogenous allopregnanolone levels for the maturation of the central nervous system and particularly for the hippocampus. Changes in neonatal allopregnanolone levels have been related to altered adult behaviour and with psychopathological susceptibility, including anxiety disorders, schizophrenia and drug abuse. However, the mechanism underlying these changes remains to be elucidated. In the present study we assessed changes in hippocampal expression of α4 and δ GABAA receptor (GABAAR) subunits as a consequence of neonatal finasteride (a 5-α reductase inhibitor) administration during early development (PD6 to PD15) in male rats. We observed that the treatment altered the temporal window of the natural peak in the expression of these subunits during development. Additionally, the level of these subunits were higher than in non-handled and control animals in the adult hippocampus. We observed that in adulthood, neonatal finasteride-treated animals presented an anxiogenic-like profile in response to progesterone administration which was absent in the rest of the groups. In conclusion, these results corroborate the relevance of neonatal maintenance of neurosteroid levels for behavioural anxiety responses in the adult, and point to some of the mechanisms involved in this alterations.

Interaction between neonatal allopregnanolone administration and early maternal separation: effects on adolescent and adult behaviors in male rat.

Endogenous neurosteroid level fluctuations are related to several emotional and behavioral alterations. Neurosteroids also have important roles during neurodevelopment, with there being a relationship between modification of their levels in neurodevelopmental periods and behavioral alterations in adolescence and adulthood. Early maternal separation (EMS) is a stressful event that also alters neurodevelopment and adolescent and adult behaviors. The aim of the present study is to analyze the interaction between the effects of the neonatal alteration of allopregnanolone (AlloP), neurosteroid that increase its levels after acute stress presentation, and EMS on adolescent exploration and adult anxiety and sensorimotor gating in male rats. AlloP (10 mg/kg s.c.) was administrated between postnatal day 5 (PN5) and PN9, and a single 24-hour period of EMS was carried out on PN9. Exploration was analyzed at PN40 and PN60. At adult age (PN85), anxiety was tested by means of the elevated plus-maze test (EPM), and sensorimotor gating by means of prepulse inhibition test (PPI). PPI deterioration has been considered as a reliable indicator of diseases such as schizophrenia. Results showed that the previous neonatal AlloP administration neutralized the effects of EMS in the adolescent exploration (increase of traveled distance and decrease of head-dips). In adult age, an anxiolytic-like profile was observed as a consequence of EMS. Finally, EMS and neonatal AlloP disrupted PPI. Taken together, these data show the important role that physiological neonatal AlloP levels and stressful events play in neural development, adult behavior and vulnerability to neurodevelopmental disorders such as schizophrenia.

Effects of early postnatal allopregnanolone administration on elevated plus maze anxiety scores in adult male Wistar rats.

BACKGROUND/AIMS: Recent findings suggest that neurosteroids are involved in brain development. The present study focused on the long-term effects of developmentally altered allopregnanolone (AlloP) levels on anxiety-like behavior in adulthood. METHOD: We administered AlloP (10 mg/kg) to rat pups once a day from the 5th to the 9th day after birth. A dose-response study on midazolam in the elevated plus maze test was carried out in adulthood (experiment 1) in order to screen GABAA-benzodiazepine function alterations. Given that the anxiety-like responses were not affected by AlloP, we doubled the initial AlloP dose (experiment 2). One group of pups was left undisturbed with their dams in order to control the effects of daily handling. Only males were behaviorally tested. RESULTS: Neonatal AlloP administration (10 mg/kg) did not alter the behavioral response to midazolam in adulthood at the doses tested. Neonatal AlloP administration at the higher dose (20 mg/kg) induced an anxiolytic-like profile in adulthood (increased entries into and time spent in the open arms), without affecting motor activity. The behavioral effects of neonatal AlloP administration were both selective and independent of daily handling. CONCLUSION: Alterations in AlloP levels during maturation could partly explain the interindividual differences shown by adult subjects in response to environmental stress.

Early postnatal neuroactive steroid manipulation differentially affects recognition memory and passive avoidance performance in male rats.

Early postnatal neuroactive steroids (NAS) play a significant role in the neurodevelopment. Their alteration can modify adult behavior, such as anxiety or learning. For this reason, we set out to observe if neonatal NAS levels alteration affects two types of learning implying low or high levels of emotional content, such as recognition memory and aversive learning respectively. Thus, we tested allopregnanolone or finasteride administered from postnatal days 5-9. In adulthood, recognition memory was assessed using the object recognition test, as well as aversive learning throughout the passive avoidance test (PA). Because of the important emotional component of PA, which can be influencing learning, we evaluated anxiety-like behavior by means of the open field test (OF). The results indicated that those animals administered with finasteride showed higher recognition levels of a familiar object. On the other hand, they showed an impairment in a stressful learning, such as PA. However, no effects of finasteride were observed on anxiety-like behavior in OF, despite it has been reported that neonatal finasteride treatment can promote an anxiety-like profile in the elevated plus-maze test in adulthood. Regarding neonatal allopregnanolone, animals showed higher levels in OF exploration only when they were already familiar with the apparatus. Furthermore, neonatal allopregnanolone did not affect recognition memory or aversive learning. In conclusion, the neonatal NAS manipulation by means of finasteride differently affected two types of learning implying distinct stress levels. Altogether, the results show the importance of the emotional content to explain the effects of neonatal NAS manipulation on learning.

Early postnatal allopregnanolone levels alteration and adult behavioral disruption in rats: Implication for drug abuse.

Several studies have highlighted the role that early postnatal levels of allopregnanolone play in the development of the CNS and adult behavior. Changes in allopregnanolone levels related to stress have been observed during early postnatal periods, and perinatal stress has been linked to neuropsychiatric disorders. The alteration of early postnatal allopregnanolone levels in the first weeks of life has been proven to affect adult behaviors, such as anxiety-related behaviors and the processing of sensory inputs. This review focuses on the first studies about the possible relationship between the early postnatal allopregnanolone levels and the vulnerability to abuse of drugs such as alcohol in adulthood, given that (1) changes in neonatal allopregnanolone levels affect novelty exploration and novelty seeking has been linked to vulnerability to drug abuse; (2) early postnatal administration of progesterone, the main allopregnanolone precursor, affects the maturation of dopaminergic meso-striatal systems, which have been related to novelty seeking and drug abuse; and (3) alcohol consumption increases plasma and brain allopregnanolone levels in animals and humans. Manipulating neonatal allopregnanolone by administering finasteride, an inhibitor of the 5α-reductase enzyme that participates in allopregnanolone synthesis, increases alcohol consumption and decreases the locomotor stimulant effects of low alcohol doses. At a molecular level, finasteride decreases dopamine and serotonin in ventral striatum and dopamine release in nucleus accumbens. Preliminary results suggest that serotonin 5HT3 receptors could also be affected. Although an in-depth study is necessary, evidence suggests that there is a relation between early postnatal allopregnanolone and vulnerability to drug use/abuse.

Early post-natal neuroactive steroid manipulation modulates ondansetron effects on initial periods of alcohol consumption in rats.

Neuroactive steroids (NS) such as allopregnanolone are crucial for brain development and adult behaviour. Early post-natal alterations of NS by administering finasteride induce a decrease in the sensitivity to stimulant effects of low alcohol doses, an increase in alcohol consumption, and a decrease in ventrostriatal dopamine and serotonin levels. The aim of the present study is to observe if the effects of the 5HT3 receptor antagonist ondansetron on initial alcohol consumption are modulated by post-natal NS manipulation. For this purpose, allopregnanolone, finasteride, or vehicle was injected from day 5 to 9. In adulthood, a novel object preference test was carried out in order to detect a possible novelty-seeking pattern in our animals, which has been related to vulnerability to drug abuse. The subjects then had access to two bottles (alcohol or control solutions) one hour daily for two consecutive weeks. Ondansetron (0.01 mg/kg, 0.1 mg/kg or vehicle) was administered before the hour of consumption in the initial phase (days 1, 2, 3) of the procedure, and after prolonged alcohol intake (days 11, 12, 13). Results indicated that finasteride animals showed a higher preference to explore the new object, as well as a higher alcohol consumption than the rest of the groups. Moreover, 0.1 mg/kg of ondansetron decreased alcohol consumption, but only in the post-natal finasteride group, suggesting a possible increase in 5HT3 receptor sensitivity in these animals. In conclusion, NS manipulation in crucial stages of development, such as early post-natal periods, seems to play an important role on the effects of ondansetron on alcohol intake and in the vulnerability to develop drug use or abuse.

Intrahippocampal allopregnanolone decreases voluntary chronic alcohol consumption in non-selected rats.

We have recently shown that 0.2 microg of the neurosteroid allopregnanolone (AlloP) administered to the hippocampus induced an anxiolytic-like profile and also reduced alcohol withdrawal symptoms in voluntary and chronic alcohol-drinking rats. The aim of the present work was to study whether the administration of this dose of AlloP could affect alcohol consumption in non-selected rats that have been voluntarily ingesting high doses of alcohol for long periods of time in a limited access procedure. We used a free-choice drinking procedure that involved providing the rats with an alcoholic solution (10% ethanol) at an early age. Alcohol and control rats were assigned randomly to three groups that received an intrahippocampal (dorsal CA1) injection before the period of alcohol consumption after a long history of chronic alcohol intake. The injection groups were AlloP (0.2 microg, 1.26 microM), pregnenolone sulfate (PregS) (5 ng, 24 microM) or vehicle. Blood alcohol concentrations (BAC) were assessed before testing the effects of injections on alcohol consumption. Although AlloP did not eliminate alcohol ingestion, it significantly decreased alcohol consumption. The intrahippocampal administration of PregS, at the dose tested, did not effectively modify alcohol consumption levels. These results indicate that the positive modulation of hippocampal GABA(A) receptors induced by neurosteroids can be an important neurobiological target for reducing chronic alcohol consumption.

Effects of neonatal and adolescent neuroactive steroid manipulation on locomotor activity induced by ethanol in male wistar rats.

Neonatal neuroactive steroids levels are crucial for brain development. Alterations of neonatal neuroactive steroids levels induce anxiolytic-like effects and improve exploration in novel environments in adulthood. These behavioural traits, i.e. sensation/novelty seeking, anxiety or impulsivity, are associated with vulnerability to drug use and abuse. Adolescence is also recognized as a particularly critical developmental phase to contribute to vulnerable phenotype. However, the influence of neuroactive steroids during development in the vulnerability to drug addiction has been poorly studied. The aim of the present experiment is to study the effect of early neonatal and adolescent manipulations of neuroactive steroids on the sensitivity to the stimulant effects of ethanol in adult male rats. Therefore, allopregnanolone or finasteride, an allopregnanolone synthesis inhibitor, were injected from postnatal day 5-9. In early adolescence, half of the subjects were injected with progesterone, the main allopregnanolone precursor, and the elevated plus-maze anxiety test was performed. Results indicated that early adolescent progesterone induced anxiolytic-like effects (increase in the percentage of entries and time in open arms). Neonatal finasteride administration decreased locomotor activity induced by ethanol in adolescent vehicle subjects. Interestingly, differences induced by neonatal treatments were not present in the animals that received progesterone in the early adolescence. In conclusion, neuroactive steroid manipulations in crucial stages of development could be playing an important role in behavioural effects of alcohol such as the sensitivity to locomotor stimulation.

Individual differences in cognitive aging: implication of pregnenolone sulfate.

In humans and animals, individual differences in aging of cognitive functions are classically reported. Some old individuals exhibit performances similar to those of young subjects while others are severely impaired. In senescent animals, we have previously demonstrated a significant correlation between the cognitive performance and the cerebral concentration of a neurosteroid, the pregnenolone sulfate (PREG-S). Neurotransmitter systems modulated by this neurosteroid were unknown until our recent report of an enhancement of acetylcholine (ACh) release in basolateral amygdala, cortex and hippocampus induced by intracerebroventricular (i.c.v.) or intracerebral administrations of PREG-S. Central ACh neurotransmission is known to be involved in the regulation of memory processes and is affected in normal aging and severely altered in human neurodegenerative pathologies like Alzheimer's disease. In the central nervous system, ACh neurotransmission is also involved in the modulation of sleep-wakefulness cycle, and particularly the paradoxical sleep (PS). Relationships between paradoxical sleep and memory are documented in the literature in old animals in which the spatial memory performance positively correlates with the basal amounts of paradoxical sleep. PREG-S infused at the level of ACh cell bodies (nucleus basalis magnocellularis, NBM, or pedunculopontine nucleus, PPT) increases paradoxical sleep in young animals.Finally, aging related cognitive dysfunctions, particularly those observed in Alzheimer's disease, have also been related to alterations of mechanisms underlying cerebral plasticity. Amongst these mechanisms, neurogenesis has been extensively studied recently. Our data demonstrate that PREG-S central infusions dramatically increase neurogenesis, this effect could be related to the negative modulator properties of this steroid at the GABA(A) receptor level. Taken together these data suggest that neurosteroids can influence cognitive processes, particularly in senescent subjects, through a modulation of ACh neurotransmission associated with paradoxical sleep modifications; furthermore, our recent data suggest a critical role for neurosteroids in the modulation of cerebral plasticity, mainly on hippocampal neurogenesis.

Neonatal finasteride administration decreases dopamine release in nucleus accumbens after alcohol and food presentation in adult male rats.

Endogenous levels of the neurosteroid (NS) allopregnanolone (AlloP) during neonatal stages are crucial for the correct development of the central nervous system (CNS). In a recent work we reported that the neonatal administration of AlloP or finasteride (Finas), an inhibitor of the enzyme 5α-reductase needed for AlloP synthesis, altered the voluntary consumption of ethanol and the ventrostriatal dopamine (DA) levels in adulthood, suggesting that neonatal NS manipulations can increase alcohol abuse vulnerability in adulthood. Moreover, other authors have associated neonatal NS alterations with diverse dopaminergic (DAergic) alterations. Thus, the aim of the present work is to analyse if manipulations of neonatal AlloP alter the DAergic response in the nucleus accumbens (NAcc) during alcohol intake in rats. We administered AlloP or Finas from postnatal day (PND) 5 to PND9. At PND98, we measured alcohol consumption using a two-bottle free-choice model (ethanol 10% (v/v)+glucose 3% (w/v), and glucose 3% (w/v)) for 12 days. On the last day of consumption, we measured the DA and 3,4-dihydroxyphenylacetic acid (DOPAC) release in NAcc in response to ethanol intake. The samples were obtained by means of in vivo microdialysis in freely moving rats, and DA and DOPAC levels were determined by means of high-performance liquid chromatography analysis (HPLC). The results revealed that neonatal Finas increased ethanol consumption in some days of the consumption phase, and decreased the DA release in the NAcc in response to solutions (ethanol+glucose) and food presentation. Taken together, these results suggest that neonatal NS alterations can affect alcohol rewarding properties.

Intrahippocampal nicotine in alcohol drinking rats--effects on lever-press response.

We have previously shown differences on learning processes between alcohol drinking and non-alcohol drinking rats. Underlying these effects, functional differences in the septo-hippocampal pathway were hypothesized. We have performed a dose-response study for intrahippocampal nicotine (CA1) on acquisition and extinction of the lever-press response and antagonization test by co-administration of mecamylamine. Results show that the administration of nicotine in CAI region has a detrimental dose-dependent effect on acquisition in alcohol drinkers, with a dose of 10 nM being the most disruptive. In the controls, only doses of 10 and 20 nM had detrimental effect. The effect of nicotine (10 nM) was partially (alcoholics) or fully (controls) antagonized by mecamylamine co-administration (30 nM). Summarizing, the alcohol groups showed a dose-response curve for nicotine shifted leftwards, and a partial antagonism of these effects by mecamylamine; these effects may be consequence of the functional sensitization of the nicotinic responsivity in the CAI region which were produced by the chronic alcohol.

Perinatal hypothyroidism effects on neuromotor competence, novelty-directed exploratory and anxiety-related behaviour and learning in rats.

Thyroid hormone is essential for proper development of the mammalian CNS. Previous studies have documented a decrease in the ability of neonatal hypothyroid animals to learn and to habituate to maze tests and an increase in spontaneous activity. However, there is little information about the effects of perinatal (i.e. perinatal and postnatal) hypothyroidism on behaviour. The aim of the present work was to investigate the longitudinal effects of perinatal hypothyroidism on certain aspects of the behaviour in rats. Neuromotor competence was tested at 21, 40 and 60 days, novelty-directed exploratory behaviour and anxiety-related behaviour were evaluated at 40 and 60 days by means of the Boissier tests and associative learning ability was tested at 80 days by means of a step-through passive avoidance task. The persistence of the effects of perinatal hypothyroidism on psychomotor performance was highly dependent on the task examined. Perinatal hypothyroidism caused an increase of locomotor activity as revealed by the total distance travelled in the Boissier test and this increase also comprised a component of decreased anxiety-related behaviour. Methimazole-treated subjects also had higher head-dip scores than controls at 40 days while no differences were observed at 60 days. Finally, our results showed that methimazole-treated rats performed poorly in a passive avoidance learning task.

Perinatal hypothyroidism effects on step-through passive avoidance task in rats.

Previous studies have documented a decrease in the ability of neonatal hypothyroid animals to learn and habituate to maze tests, and an increase in spontaneous activity. However, there is little information about the effects of perinatal (i.e., prenatal and postnatal) hypothyroidism on behaviour. The present study was designed to assess whether perinatal hypothyroidism in rats induces alteration on acquisition and/or short- and long-term retention of a learned response in male Wistar rats. Perinatal hypothyroidism was induced by prolonged (E9-P21) exposure of pregnant and lactating dams to methimazole (administered orally in drinking water, 0.2 mg/ml). Cognitive function was tested at 50 days by means of a step-through passive avoidance task. The effects of perinatal hypothyroidism on the retention of the passive avoidance response are long lasting being, however, highly dependent on the retention after the original training. Our results showed that methimazole-treated rats performed more poorly when retention was tested at long-term (24 h and 7 days) retention interval. Instead, methimazole-treated rats showed longer retrieval latencies than the control ones did when retention was tested at short term (1 h).

Effects of chronic dysthyroidism on activity and exploration.

The aim of the present study was to determine the influence of thyroid function on the activity and exploratory behaviour of male Wistar rats. Dysthyroidism was induced by adding drugs to their drinking water from the ninth day of gestation. This method is not as stressful as daily thyroxine injections or thyroidectomy, and therefore did not affect the analysed behavioural patterns. After weaning, the drugs were administered to the young rats until the end of the experiment. Activity and exploration were measured using the Boissier test, a light-darkness test and an open-field test when they were 77 days old. In order to verify that the animals' motor capacity had not been impaired, a psychomotor battery was used. Chronic hyperthyroidism produced a significant increase in activity, but did not affect exploration. On the other hand, hypothyroidism did not affect activity, but did increase exploration. This increase in exploration was observed in activity-independent behavioural parameters, such as head dipping and glancing.

Tolerance and sensitization to the hypnotic effects of alcohol induced by chronic voluntary alcohol intake in rats.

The effect of a chronic alcohol exposure on the development of tolerance to the depressive effects of alcohol were examined in male Wistar rats that voluntary self-administered alcohol. A free-choice drinking procedure based on the limited access paradigm and the addition of glucose that implies an early availability of the alcoholic solution was used (Alcoholism Primary Praecox procedure). Alcohol induced sleep time (3.5 g alcohol per kg i.p.) was measured at 90 days (after 2 months of alcohol consumption) or at 60 + 90 days old (1 or 2 months of alcohol consumption). The psychomotor performance was also evaluated by means of an 80 degrees inclined screen test. Subjects that had been tested for the hypnotic effects at both 60 and 90 days showed a higher intake of alcoholic solution than the animals only tested at 90 days. The same consumption increase was observed in the glucose group. No significant differences between groups were observed in the inclined screen test. Tolerance to the hypnotic effects of alcohol was observed at 90 days. On the other hand, no significant differences between alcohol and control groups (glucose or water) were observed in the sleep time at 60 days. In the alcohol-drinking rats tested for two trials (60 and 90 days), sensitization instead of tolerance to the second hypnotic alcohol injection was seen. Tolerance to the hypnotic effects of alcohol observed after chronic voluntary alcohol consumption may provide animal models of alcoholism based on limited access to sweetened alcoholic solutions with construct validity.

Effects of voluntary alcohol intake on nicotine-induced behavioural sensitisation in rats.

Behavioural sensitisation has been suggested to play a role in the acquisition and maintenance of addictive behaviour. The aim of the present study was to assess nicotine-induced behavioural sensitisation in chronic voluntary alcohol drinking rats. Subjects had free access to alcohol/water or glucose/water solutions since weaning. Rats were pretreated after 2 months of voluntary alcohol drinking. Pretreatment consisted of once-daily intraperitoneal injection of nicotine (0.5 mg/kg) or saline administered for five consecutive days. The nicotine-induced behavioural sensitisation of locomotor activity was tested 3 weeks latter. Horizontal motor activity was monitored for 30 min and expressed as distance travelled (in centimetres). During all the experimental procedure, the animals were maintained under 1-h limited access to alcohol. In glucose-drinking animals, results indicated that nicotine induced locomotor activity sensitization: The locomotor effects of nicotine challenge in the nicotine-pretreated group of rats were significantly enhanced as compared with the saline-pretreated group (Duncan, P<.01). Instead, in the alcohol-drinking animals, no significant differences were observed between the nicotine- and saline-pretreated groups. Thus, chronic alcohol consumption at mild doses prevented the development and/or the long-term expression of the nicotine-induced sensitisation at the doses tested.

Effects of dysthyroidism in plus maze and social interaction tests.

The aim of the present study was to determine the influence of thyroid hormones on the anxiety of male Wistar rats. Dysthyroidism was induced by adding 20 mg of methimazole (100 ml) to their drinking water or by adding 0.3 mg of L-thyroxine (100 ml) to their drinking water from the ninth day of gestation. After weaning, the drugs were administered to young rats until the end of the experiment. Anxious behavior was measured using the elevated plus maze and social interaction tests when the animals were 85 days old. Chronic methimazole administration produced a significant anxiolytic pattern in both tests. In the plus maze test, the methimazole-treated animals entered and remained more time in the open arms than the control animals. In the social interaction test, they spent more time in bodily contact, and did this more frequently than those in the control group did. Results from this experiment suggest that chronic thyroid deficiency produces an anxiolytic-like effect in both tests.

Neonatal allopregnanolone or finasteride administration modifies hippocampal K(+) Cl(-) co-transporter expression during early development in male rats.

The maintenance of levels of endogenous neurosteroids (NS) across early postnatal development of the brain, particularly to the hippocampus, is crucial for their maturation. Allopregnanolone (Allop) is a NS that exerts its effect mainly through the modulation of the GABAA receptor (GABAAR). During early development, GABA, acting through GABAAR, that predominantly produces depolarization shifts to hyperpolarization in mature neurons, around the second postnatal week in rats. Several factors contribute to this change including the progressive increase of the neuron-specific K(+)/Cl(-) co-transporter 2 (KCC2) (a chloride exporter) levels. Thus, we aimed to analyze whether a different profile of NS levels during development is critical and can alter this natural progression of KCC2 stages. We administrated sustained Allop (20mg/kg) or Finasteride (5α-reductase inhibitor, 50mg/kg) from the 5th postnatal day (PD5) to PD9 and assessed changes in the hippocampal expression of KCC2 at transcript and protein levels as well as its active phosphorylated state in male rats. Taken together data indicated that manipulation of NS levels during early development influence KCC2 levels and point out the importance of neonatal NS levels for the hippocampal development.