Effects of acute alcohol intoxication on pituitary-gonadal axis hormones, pituitary-adrenal axis hormones, beta-endorphin and prolactin in human adolescents of both sexes

Teenage drinking continues to be a major problem in industrialized countries, where almost 35% of alcohol drinkers are under 16 years old. In the present paper we studied the effects of acute alcohol intoxication (AAI) on the pituitary-gonadal (PG) axis hormones, and the possible contribution of pituitary-adrenal (PA) axis hormones, beta-endorphin (BEND), and prolactin (PRL) to the alcohol-induced dysfunction of PG axis hormones. Blood samples were drawn from adolescents that arrived at the emergency department with evident behavioral symptoms of drunkenness (AAI) or with nil consumption of alcohol (controls [C]). Our results demonstrated that AAI produces in adolescents a high increase in plasma PRL, ACTH, and cortisol (F), and a contradictory behavior of testosterone (T) according to gender: plasma T was increased in females and decreased in males. ACTH and PRL correlated positively with F, dehydroepiandrosterone-sulphate (DHEAS) and T in females, which suggests that PRL and ACTH could synergistically stimulate adrenal androgen production. In contrast, the decrease in T and increase in BEND in males suggests that AAI could have an inhibitory effect on testicular T, perhaps mediated by BEND. The hormones studied are involved in the development of secondary sexual characteristics and the growth axis during adolescence. The deleterious effects of alcohol abuse should be made known to adolescents and the appropriate authorities.     

Effects of Voluntary Alcohol Intake on Risk Preference and Behavioral Flexibility during Rat Adolescence

Alcohol use is common in adolescence, with a large portion of intake occurring during episodes of binging. This pattern of alcohol consumption coincides with a critical period for neurocognitive development and may impact decision-making and reward processing. Prior studies have demonstrated alterations in adult decision-making following adolescent usage, but it remains to be seen if these alterations exist in adolescence, or are latent until adulthood. Here, using a translational model of voluntary binge alcohol consumption in adolescents, we assess the impact of alcohol intake on risk preference and behavioral flexibility during adolescence. During adolescence (postnatal day 30–50), rats were given 1-hour access to either a 10% alcohol gelatin mixture (EtOH) or a calorie equivalent gelatin (Control) at the onset of the dark cycle. EtOH consuming rats were classified as either High or Low consumers based on intake levels. Adolescent rats underwent behavioral testing once a day, with one group performing a risk preference task, and a second group performing a reversal-learning task during the 20-day period of gelatin access. EtOH-High rats showed increases in risk preference compared to Control rats, but not EtOH-Low animals. However, adolescent rats did a poor job of matching their behavior to optimize outcomes, suggesting that adolescents may adopt a response bias. In addition, adolescent ethanol exposure did not affect the animals'' ability to flexibly adapt behavior to changing reward contingencies during reversal learning. These data support the view that adolescent alcohol consumption can have short-term detrimental effects on risk-taking when examined during adolescence, which does not seem to be attributable to an inability to flexibly encode reward contingencies on behavioral responses.     

Molecular mechanisms responsible for alcohol-induced myopathy in skeletal muscle and heart

Chronic alcohol abuse has the potential to modulate striated muscle physiology and function. The skeletal muscle alcoholic myopathy is characterized by muscle weakness and difficulties in gait and locomotion, while chronic alcohol consumption ultimately leads to a decrease in cardiac contractility and output. In both tissues a loss of protein mass results in part from a decreased protein synthesis that initially manifests as a defect in translational efficiency. This review focuses on recent developments in understanding the cellular and molecular mechanisms by which alcohol impairs mRNA translation in skeletal and cardiac muscle, including identification of the signaling pathways and biochemical sites negatively impacted. Defective signaling potentially results from resistance to the normal stimulating effects of anabolic hormones (insulin and insulin-like growth factor-I) and nutrients (leucine) as well as increased production of several negative regulators of muscle mass. Overall, the biochemical mechanisms contributing to the pathogenesis of loss of skeletal and cardiac muscle are reviewed.     

Alcohol myopathy: impairment of protein synthesis and translation initiation

Alcohol consumption leads to numerous morphological, biochemical and functional changes in skeletal and cardiac muscle. One such change observed in both tissues after either acute alcohol intoxication or chronic alcohol consumption is a characteristic decrease in the rate of protein synthesis. A decrease in translation efficiency appears to be responsible for at least part of the reduction. This review highlights advances in determining the molecular mechanisms by which alcohol impairs protein synthesis and places these observations in context of earlier studies on alcoholic myopathy. Both acute and chronic alcohol administration impairs translational control by modulating various aspects of peptide-chain initiation. Moreover, this alcohol-induced impairment in initiation is associated with a decreased availability of eukaryotic initiation factor (eIF) 4E in striated muscle, as evidenced by an increase in the amount of the inactive eIF4E.4E-BP1 complex and decrease in the active eIF4E.eIF4G complex. In contrast, alcohol does not produce consistent alterations in the control of translation initiation by the eIF2 system. The etiology of these changes remain unresolved. However, defects in the availability or effectiveness of various anabolic hormones, particularly insulin-like growth factor-I, are consistent with the alcohol-induced decrease in protein synthesis and translation initiation.     

Human skin: an independent peripheral endocrine organ

The historical picture of the endocrine system as a set of discrete hormone-producing organs has been substituted by organs regarded as organized communities in which the cells emit, receive and coordinate molecular signals from established endocrine organs, other distant sources, their neighbors, and themselves. In this wide sense, the human skin and its tissues are targets as well as producers of hormones. Although the role of hormones in the development of human skin and its capacity to produce and release hormones are well established, little attention has been drawn to the ability of human skin to fulfil the requirements of a classic endocrine organ. Indeed, human skin cells produce insulin-like growth factors and -binding proteins, propiomelanocortin derivatives, catecholamines, steroid hormones and vitamin D from cholesterol, retinoids from diet carotenoids, and eicosanoids from fatty acids. Hormones exert their biological effects on the skin through interaction with high-affinity receptors, such as receptors for peptide hormones, neurotransmitters, steroid hormones and thyroid hormones. In addition, the human skin is able to metabolize hormones and to activate and inactivate them. These steps are overtaken in most cases by different skin cell populations in a coordinated way indicating the endocrine autonomy of the skin. Characteristic examples are the metabolic pathways of the corticotropin-releasing hormone/propiomelanocortin axis, steroidogenesis, vitamin D, and retinoids. Hormones exhibit a wide range of biological activities on the skin, with major effects caused by growth hormone/insulin-like growth factor-1, neuropeptides, sex steroids, glucocorticoids, retinoids, vitamin D, peroxisome proliferator-activated receptor ligands, and eicosanoids. At last, human skin produces hormones which are released in the circulation and are important for functions of the entire organism, such as sex hormones, especially in aged individuals, and insulin-like growth factor-binding proteins. Therefore, the human skin fulfils all requirements for being the largest, independent peripheral endocrine organ.     

Repeated alcohol administration during adolescence causes changes in the mesolimbic dopaminergic and glutamatergic systems and promotes alcohol intake in the adult rat

Adolescence is a developmental period which the risk of drug and alcohol abuse increases. Since mesolimbic dopaminergic system undergoes developmental changes during adolescence, and this system is involved in rewarding effects of drugs of abuse, we addressed the hypothesis that ethanol exposure during juvenile/adolescent period over-activates mesolimbic dopaminergic system inducing adaptations which can trigger long-term enduring behavioural effects of alcohol abuse. We treated juvenile/adolescent or adult rats with ethanol (3 g/kg) for two-consecutive days at 48-h intervals over 14-day period. Here we show that intermittent ethanol treatment during the juvenile/adolescence period alters subsequent ethanol intake. In vivo microdialysis demonstrates that ethanol elicits a similar prolonged dopamine response in the nucleus accumbens of both adolescent and adult animals pre-treated with multiple doses of ethanol, although the basal dopamine levels were higher in ethanol-treated adolescents than in adult-treated animals. Repeated ethanol administration also down-regulates the expression of DRD2 and NMDAR2B phosphorylation in prefrontal cortex of adolescent animals, but not of adult rats. Finally, ethanol treatment during adolescence changes the acetylation of histones H3 and H4 in frontal cortex, nucleus accumbens and striatum, suggesting chromatin remodelling changes. In summary, our findings demonstrate the sensitivity of adolescent brain to ethanol effects on dopaminergic and glutamatergic neurotransmission, and suggest that abnormal plasticity in reward-related processes and epigenetic mechanisms could contribute to the vulnerability of adolescents to alcohol addiction.     

ANS: aberrant neurodevelopment of the social cognition network in adolescents with autism spectrum disorders

Background

Autism spectrum disorders (ASD) are characterized by aberrant neurodevelopment. Although the ASD brain undergoes precocious growth followed by decelerated maturation during early postnatal period of childhood, the neuroimaging approach has not been empirically applied to investigate how the ASD brain develops during adolescence.

Methodology/Principal Findings

We enrolled 25 male adolescents with high functioning ASD and 25 typically developing controls for voxel-based morphometric analysis of structural magnetic resonance image. Results indicate that there is an imbalance of regional gray matter volumes and concentrations along with no global brain enlargement in adolescents with high functioning ASD relative to controls. Notably, the right inferior parietal lobule, a role in social cognition, have a significant interaction of age by groups as indicated by absence of an age-related gain of regional gray matter volume and concentration for neurodevelopmental maturation during adolescence.

Conclusions/Significance

The findings indicate the neural correlates of social cognition exhibits aberrant neurodevelopment during adolescence in ASD, which may cast some light on the brain growth dysregulation hypothesis. The period of abnormal brain growth during adolescence may be characteristic of ASD. Age effects must be taken into account while measures of structural neuroimaging have been clinically put forward as potential phenotypes for ASD.     

Mild calorie restriction does not affect testosterone levels and testicular gene expression in mutant mice

The hypothalamic-pituitary-gonadal (HPG) axis and the somatotropic axis are influenced by nutritional factors. Calorie restriction (CR) extends lifespan but suppresses both the HPG and the somatotropic axes. Since most CR studies use a fairly severe (40%-60%) reduction of calorie intake, we hypothesized that a milder CR (20%) might not be deleterious to reproduction in male mice. To test this hypothesis, we evaluated the effects of 20% CR on testicular testosterone content and on testicular expression of genes that are relevant to testicular function and reproductive competence, including insulin-like growth factor-I, cytochrome P450 aromatase (Cyp19a1), androgen receptor, luteinizing hormone receptor, follicle-stimulating hormone receptor, cytochrome P450c17 and 3-beta-hydroxysteroid dehydrogenase/isomerase. To relate CR effects to the activity of the somatotropic axis, we have used growth hormone-resistant GHR knockout mice as well as transgenic mice overexpressing GH. Mild CR did not affect testosterone levels in testis homogenates and had little effect on expression of the examined genes in the reproductive organs. Altered activity of the GH/insulin-like growth factor-1 axis had a major impact on the parameters analyzed. The results also suggest that expression of several key genes involved in the control of testicular function is preserved under conditions of mild CR and encourage speculation that mild regimens of CR can produce longevity benefits without impairing reproduction.     

The impact of exercise on thyroid hormone metabolism in children and adolescents.

Thyroid hormones are important regulators of energy metabolism and may influence energy processes during physical exercise. There are controversial results concerning thyroid hormone metabolism during strenuous exercise in adult athletes and only scant data concerning the impact of strenuous exercise on thyroid hormone metabolism in children and adolescents. Although some studies demonstrate a transient change in thyroid hormones during intense physical performance, most studies agree that these changes are of minor impact, practically reflecting the relative negative energy balance during strenuous exercise. This state of hypometabolism during intense physical performance has also been confirmed in highly trained female young athletes, who may be also characterized by reproductive axis dysfunction, manifested either as luteal-phase deficiency or amenorrhea, alongside the typical constellation of low T3, insulin and leptin levels. More importantly, strenuous exercise during childhood or adolescence is mostly accompanied by a delay of skeletal maturation, and height and may have a long-lasting negative effect on growth and acquisition of maximum bone mass. In conclusion, although thyroid hormones are only transiently or insignificantly changed during strenuous exercise, adequate caloric intake should be guaranteed in highly performing young athletes in order to counteract the relative negative energy balance and prevent alterations in endocrine-metabolic profile. Moreover, when growth and pubertal progression in very young athletes are significantly impaired, a reduction in the intensity of the physical exercise should be advocated in order to guarantee better final height and adequate acquisition of bone mass.     

Anabolic androgenic steroids differentially affect social behaviors in adolescent and adult male Syrian hamsters

Anabolic androgenic steroids (AAS) are synthetic derivatives of testosterone used by over half a million adolescents in the United States for their tissue-building potency and performance-enhancing effects. AAS also affect behavior, including reports of heightened aggression and changes in sexual libido. The expression of sexual and aggressive behaviors is a function of complex interactions among hormones, social context, and the brain, which is extensively remodeled during adolescence. Thus, AAS may have different consequences on behavior during adolescence and adulthood. Using a rodent model, these studies directly compared the effects of AAS on the expression of male sexual and aggressive behaviors in adolescents and adults. Male Syrian hamsters were injected daily for 14 days with either vehicle or an AAS cocktail containing testosterone cypionate (2 mg/kg), nandrolone decanoate (2 mg/kg), and boldenone undecylenate (1 mg/kg), either during adolescence (27-41 days of age) or in adulthood (63-77 days of age). The day after the last injection, males were tested for either sexual behavior with a receptive female or agonistic behavior with a male intruder. Adolescent males treated with AAS showed significant increases in sexual and aggressive behaviors relative to vehicle-treated adolescents. In contrast, AAS-treated adults showed significantly lower levels of sexual behavior compared with vehicle-treated adults and did not show heightened aggression. Thus, adolescents, but not adults, displayed significantly higher behavioral responses to AAS, suggesting that the still-developing adolescent brain is more vulnerable than the adult brain to the adverse consequences of AAS on the nervous system and behavior.     

(−)-Epigallocatechin gallate inhibits growth and activation of the VEGF/VEGFR axis in human colorectal cancer cells

(?)-Epigallocatechin gallate (EGCG), the major constituent of green tea, inhibits the growth of colorectal cancer cells by inhibiting the activation of various types of receptor tyrosine kinases (RTKs). The RTK vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) axis induces tumor angiogenesis in colorectal cancer. This study examined the effects of EGCG on the activity of the VEGF/VEGFR axis and the expression of hypoxia-inducible factor (HIF)-1α, which promotes angiogenesis by elevating VEGF levels, in human colorectal cancer cells. Total and phosphorylated (i.e., activated) form (p-VEGFR-2) of VEGFR-2 proteins were overexpressed in a series of human colorectal cancer cell lines. Within 3 h, EGCG caused a decrease in the expression of HIF-1α protein and VEGF, HIF-1α, insulin-like growth factor (IGF)-1, IGF-2, epidermal growth factor (EGF), and heregulin mRNAs in SW837 colorectal cancer cells, which express a constitutively activated VEGF/VEGFR axis. A decrease was also observed in the expression of VEGFR-2, p-VEGFR-2, p-IGF-1 receptor, p-ERK, and p-Akt proteins within 6 h after EGCG treatment. Drinking EGCG significantly inhibited the growth of SW837 xenografts in nude mice, and this was associated with the inhibition of the expression and activation of VEGFR-2. The consumption of EGCG also inhibited activation of ERK and Akt, both of which are downstream signaling molecules of the VEGF/VEGFR axis, and reduced the expression of VEGF mRNA in xenografts. These findings suggest that EGCG may exert, at least in part, growth-inhibitory effects on colorectal cancer cells by inhibiting the activation of the VEGF/VEGFR axis through suppressing the expression of HIF-1α and several major growth factors. EGCG may therefore be useful in the chemoprevention and/or treatment of colorectal cancer.     

Physiological effects of nonthyroidal illness syndrome in patients after cardiac surgery

In a prospective randomized placebo-controlled study, we assessed potential physiological effects of nonthyroidal illness syndrome (NTIS) in acute illness. Coronary artery bypass graft surgery was employed as a prospective model of acute illness and NTIS. Triiodothyronine (T(3)) or placebo was infused for 24 h after surgery, with a T(3) dose selected to maintain postoperative serum T(3) concentrations at preoperative levels. Patients were evaluated before coronary artery bypass graft and during the postoperative period. Cardiovascular function was monitored with Swan-Ganz catheter measurements and ECG. Urinary nitrogen excretion and L-[1-(13)C]leucine flux were used to evaluate protein metabolism. Serum measurements of relevant hormones, iron, and total iron-binding capacity were used to assess effects on sex steroid, growth hormone axis, and iron responses to illness. Cardiovascular function was not affected by T(3) infusion, except for a transient higher cardiac index in the T(3) group 6 h after surgery (3.04 +/- 0.12 for T(3) and 2.53 +/- 0.08 for placebo, P = 0.0016). Protein metabolism was not affected; changes in urinary nitrogen excretion and L-[1-(13)C]leucine flux were equivalent in the two groups (P = 0.35 and P = 0.95, respectively). No differences were observed in changes in testosterone, estrogens, growth hormone, insulin-like growth hormone I, iron, or total iron-binding capacity between T(3) and placebo groups. We conclude that, in the early stages of major illness, the decrease in circulating T(3) concentrations in NTIS has only a minimal transient physiological impact on cardiac function and plays no significant role in protecting against protein catabolism or modulating other endocrine responses or iron responses to illness.     

Effects of ginseng ingestion on growth hormone, testosterone, cortisol, and insulin-like growth factor 1 responses to acute resistance exercise

Ginseng, an herbal plant, has been ingested by many athletes in Oriental regions of the world in order to improve stamina and to facilitate rapid recovery from injuries. However, adequate investigation has not been conducted to examine the ergogenic effects of ginseng. To examine the effects of ginseng supplements on hormonal status following acute resistance exercise, eight male college students were randomly given water (control; CON) or 20 g of ginseng root extract (GIN) treatment immediately after a standardized exercise bout. Venous blood samples were drawn before and immediately after exercise and at 4 time points during a 2-hour recovery period. Human growth hormone, testosterone, cortisol, and insulin-like growth factor 1 (IGF-1) levels were determined by radioimmunoassay. The responses of plasma hormones following ginseng consumption were not significant between CON and GIN treatments during the 2-hour recovery period. These results do not support the use of ginseng to promote an anabolic hormonal status following resistance exercise.     

Pubertal maturation modifies the regulation of insulin-like growth factor-I receptor signaling by estradiol in the rat prefrontal cortex

The transition from adolescence to adulthood is accompanied by substantial plastic modifications in the cerebral cortex, including changes in the growth and retraction of neuronal processes and in the rate of synaptic formation and neuronal loss. Some of these plastic changes are prevented in female rats by prepubertal ovariectomy. The ovarian hormone estradiol modulates neuronal differentiation and survival and these effects are in part mediated by the interaction with insulin-like growth factor-I (IGF-I). In this study, we have explored whether the activation by estradiol of some components of IGF-I receptor signaling is altered in the prefrontal cortex during puberty. Estradiol administration to rats ovariectomized after puberty resulted, 24 h after the hormonal administration, in a sustained phosphorylation of Akt and glycogen synthase kinase 3 beta in the prefrontal cortex. However, this hormonal effect was not observed in animals ovariectomized before puberty. These findings suggest that during pubertal maturation there is a programming by ovarian hormones of the future regulatory actions of estradiol on IGF-I receptor signaling in the prefrontal cortex. The modification in the regulation of IGF-I receptor signaling by estradiol during pubertal maturation may have implications for the developmental changes occurring in the prefrontal cortex in the transition from adolescence to adulthood.     

Neuroendocrine regulation of somatic growth in fishes

Growth is a polygenic trait that is under the influence of multiple physiological pathways regulating energy metabolism and muscle growth.Among the possible growth-regulating pathways in vertebrates,components of the somatotropic axis are thought to have the greatest influence.There is growing body of literature focusing on the somatotropic axis and its role regulating growth in fish.This includes research into growth hormone,upstream hypothalamic hormones,insulin-like growth factors,and downstream signaling molecules.Many of these signals have both somatic effects stimulating the growth of tissues and metabolic effects that play a role in nutrient metabolism.Signals of other endocrine axes exhibit profound effects on the function of the somatotropic axis in vivo.In this review we highlight recent advances in our understanding of the teleost fish endocrine somatotropic axis,including emerging research using genetic modified models.These studies have revealed new aspects and challenges associated with regulation of the important steps of somatic growth.     

Growth factor-mediated regulation of aromatase activity in human skin fibroblasts.

We investigated the effects of various hormones and growth factors on aromatase activity in cultured human skin fibroblasts. Several potential trophic factors were tested for their ability to modify basal aromatase activity or the response to dibutyryladenosine 3',5'-cyclic monophosphate and dexamethasone because (i) no endogenous ligand has been identified that is responsible for stimulating aromatase activity in the periphery, and (ii) dexamethasone and cAMP analogs can increase this enzyme's activity in fibroblasts. The effect of insulin and insulin-like growth factors were examined in closer detail because of the clinical association between insulin and hyperandrogenism. Pituitary hormones and hypothalamic releasing factors, such as human ACTH (10 nM), beta-endorphin (10 nM), beta-lipotropin (10 nM), alpha-MSH (10 nM), gamma 3-MSH (10 nM), ovine luteinizing hormone (10 ng/ml), ovine follicle-stimulating hormone (10 ng/ml), ovine thyroid-stimulating hormone (10 ng/ml), rat growth hormone (10 ng/ml), rat prolactin (10 ng/ml), rat corticotropin-releasing factor (10 nM), luteinizing hormone-releasing factor (10 nM), thyrotropin-releasing factor (10 nM), human growth hormone-releasing factor (10 nM), and somatostatin (10 nM), have no significant effects on aromatase activity. Porcine inhibin A (10 ng/ml) and porcine activin AB (10 ng/ml), two ovarian hormones with structural transforming homology to transforming growth factor-beta, also have no effect on aromatase activity. Although basic fibroblast growth factor (1-100 ng/ml), acidic fibroblast growth factor (1 ng/ml), epidermal growth factor (1 ng/ml), platelet-derived growth factor (1 ng/ml), tumor necrosis factor (1 ng/ml), and transforming growth factor-beta 1 (1 ng/ml) have no effect on basal aromatase activity in human skin fibroblasts, all of these growth factors inhibited the ability of dibutyryladenosine 3',5'-cyclic monophosphate to stimulate aromatase activity. In contrast, both insulin (100 pg/ml-10 ng/ml) and insulin-like growth factor-1 (1-100 ng/ml) had no effect on cAMP-stimulated aromatase but potentiated the action of dexamethasone (100 nM). Thus, there is a clear distinction between the effects of dexamethasone and cAMP on peripheral aromatase. On the basis of the results presented here, it is interesting to speculate that the hyperandrogenism that is often associated with insulin resistance may be due to a combination of growth factor-mediated inhibition of aromatase activity and the failure of peripheral tissues to respond to insulin and metabolize androgens to estrogens.     

Hormonal Correlates of Divergent Growth Trajectories in Wild Male Anubis (Papio anubis) and Hamadryas (P. hamadryas) Baboons in the Awash River Valley, Ethiopia

Comparative investigations of hormone concentration and pattern during ontogeny can offer insight regarding the evolution of growth trajectories. Anubis (Papio anubis) and hamadryas (P. hamadryas) baboons exemplify primate populations at a crucial stage of phylogenetic divergence. Though not reproductively isolated, the species are distinguished by consistent morphological, behavioral, and physiological differences, including trajectories of growth and maturation associated with divergent male reproductive strategies. As a step toward understanding the proximate causes of these differences, we tested several hypotheses regarding the relationship of growth-regulatory hormones and binding proteins (insulin-like growth factor-I, insulin-like growth factor binding protein-3 [IGFBP-3], growth hormone binding protein, and testosterone) to growth in several measurements. We collected samples (N = 559) across 13 field seasons, from 7 different social groups. Samples came from 398 different individuals. We sampled 285 once; 76, twice; 29, three times; 5, four times; and 3, five times. Although ages at peak hormone concentrations were not significantly different, concentrations of all hormones and binding proteins measured, except testosterone, were higher in hamadryas than in anubis. All factors measured correlated positively with growth in both species, and IGFBP-3 and testosterone in particular correlated significantly with growth in all measurements. Overall, our findings suggest a role for the growth hormone/insulin-like growth factor axis in producing distinctive patterns of growth in these species.     

Effects of Acute or Chronic Ethanol Exposure during Adolescence on Behavioral Inhibition and Efficiency in a Modified Water Maze Task

Ethanol is well known to adversely affect frontal executive functioning, which continues to develop throughout adolescence and into young adulthood. This is also a developmental window in which ethanol is misused by a significant number of adolescents. We examined the effects of acute and chronic ethanol exposure during adolescence on behavioral inhibition and efficiency using a modified water maze task. During acquisition, rats were trained to find a stable visible platform onto which they could escape. During the test phase, the stable platform was converted to a visible floating platform (providing no escape) and a new hidden platform was added in the opposite quadrant. The hidden platform was the only means of escape during the test phase. In experiment 1, adolescent animals received ethanol (1.0g/kg) 30min before each session during the test phase. In experiment 2, adolescent animals received chronic intermittent ethanol (5.0g/kg) for 16 days (PND30 To PND46) prior to any training in the maze. At PND72, training was initiated in the same modified water maze task. Results from experiment 1 indicated that acute ethanol promoted behavioral disinhibition and inefficiency. Experiment 2 showed that chronic intermittent ethanol during adolescence appeared to have no lasting effect on behavioral disinhibition or new spatial learning during adulthood. However, chronic ethanol did promote behavioral inefficiency. In summary, results indicate that ethanol-induced promotion of perseverative behavior may contribute to the many adverse behavioral sequelae of alcohol intoxication in adolescents and young adults. Moreover, the long-term effect of adolescent chronic ethanol exposure on behavioral efficiency is similar to that observed after chronic exposure in humans.     

Thyroid hormone levels in rats exposed to alcohol during development

Maternal ingestion of alcohol appears to cause a pattern of congenital anomalies with a reduction of pre- and postnatal growth in the offspring. In order to study the possible implication of thyroid function in the effects of pre- and/or postnatal exposure to alcohol, we have studied serum thyroxine (T4) and triiodothyronine (T3) levels in rats from alcohol-fed mothers during the postnatal period (0-50 days). Blood alcohol levels of ethanol-treated pregnant rats were approximately equal to 20-25 mM and their serum T4 levels were decreased, compared with the pair-fed controls, at 15 and 21 days of gestation. No significant changes were observed in T3 levels. Prenatal alcohol exposure was associated with a decrease in both T4 and T3 levels in pups at birth. Although T4 levels continued reduced in the 40-50 days of the postnatal period, no clear effects were observed on T3 levels during this time. Moreover, the more marked alterations were obtained when the offspring were postnatally and pre + postnatally exposed to alcohol. Significant decreases were found in both T4 and T3 levels following postnatal exposure, except at the 20-25th day when a marked but transient increase in T4 levels was observed. These results indicate that alcohol exposure disturbs the hypothalamo-pituitary-thyroid axis, as measured by T3 and T4 hormone levels, mainly when the rats are exposed during the postnatal period.