Juan Carlos Jorge

Modulation of elevated plus maze behavior after chronic exposure to the anabolic steroid 17α-methyltestosterone in adult mice

Exposure to supraphysiological doses of androgens may disrupt affective components of behavior. In this study, behavior of adult C57Bl/6 male mice was studied after exposure to the anabolic androgenic steroid (AAS) 17alpha-methyltestosterone (17alpha-meT; 7.5 mg/kg) via a subcutaneous osmotic pump for 17 days. Controls received vehicle implants (0.9% NaCl + 30% cyclodextrine). On day 15, experimental animals were challenged with an ethanol (EtOH) injection (i.p.; 1 g/kg) while controls received saline injections. Five minutes after the injection, animals were tested in an automated elevated plus maze (EPM) or in automated activity chambers. In addition, injection-free animals were tested for ethanol consumption on day 16 after an overnight water deprivation period. Whereas chronic exposure to 17alpha-meT did not modulate open arm behavior, EtOH-exposed animals made more entries into the open arms than controls (P < 0.05). A significant reduction of risk assessment behaviors (rearing, flat approach behavior, and stretch attended posture) over the EPM was noted for EtOH-exposed animals whereas a reduction in stretch attended postures was observed among 17alpha-meT-exposed animals. Locomotor activity, and light-dark transitions in activity chambers remained unaltered. Exposure to AAS did not modulate EtOH consumption. Our data suggest that exposure to a supraphysiological dose of 17alpha-meT has minimal effects on exploratory-based anxiety.

A testosterone metabolite is rewarding to ovariectomized female rats.

Anabolic androgenic steroids have become a major class of drugs of abuse among a growing population of male and female adolescents. Although the rewarding and reinforcing properties of androgens have been demonstrated in male rodents, it is unknown whether these properties are apparent in female rats. In this study, conditioned place preference and self-administration paradigms showed that the endogenous androgen metabolite 3alphaDIOL is rewarding and reinforcing in ovariectomized female rats. Because 3alphaDIOL can be synthesized de novo in the brain, it is hypothesized that this neurosteroid provides a permissive neurochemical environment that modulates reward processes.

Modulation of Affect After Chronic Exposure to the Anabolic Steroid 17α-Methyltestosterone in Adult Mice.

A battery of behavioral tasks in C57BL/6J mice was used to assess changes in affective components of behavior after systemic exposure to the anabolic-androgenic steroid (AAS) 17alpha-methyltestosterone (7.5 mg/kg). Gonadal weight in both sexes was reduced after 16 days of AAS exposure. Changes in discrete components of social behaviors were observed. No changes were recorded in the elevated plus-maze, the light-dark transition, and defensive behavior tests on exposure to 17alpha-methyltestosterone. When compared with controls, AAS-exposed females received a greater number of shocks, and AAS-exposed males displayed a shorter recovery time to consume water after a negative reinforcer in the modified Vogel conflict test. Results show that systemic exposure to a single AAS modified social behaviors, whereas minimal effects on anxiety-related behaviors were observed according to sex.

The neurosteroid 3αDIOL modulates place preference when infused in the basolateral amygdala according to sex

Three different behavioral tasks were used to study the role of the neurosteroid 5alpha -androstane-3alpha, 17beta-diol (3alphaDIOL) in affective components of behavior when infused into the basolateral amygdala (BLA) of both sexes. Female rats were ovariectomized; half received implants containing estradiol benzoate (OVX-EB), whereas the other half received empty implants (OVX). Male rats were gonadally intact. No differences were noted in male behavior according to the conditioned place preference (CPP) test, the modified Vogel conflict test (VCT), or the elevated plus maze (EPM) upon infusion of 3alphaDIOL. In contrast, 3alphaDIOL modulated CPP and VCT performance among female rats. Therefore, the authors propose that 3alphaDIOL modulates affect through the BLA via a sex-specific mechanism.

Sex-specific modulation of anxiety and locomotion after neonatal exposure to pregnenolone sulfate

Neurosteroids may influence adult behavior and endocrine function since early in development. To test this hypothesis, Sprague-Dawley pups from both sexes were injected with pregnenolone sulfate (PREG-S) from postnatal (PN) day 1 to 14. Pubertal onset in females was determined by monitoring the day of vaginal opening. After vaginal opening, the pattern of estrous cycle was monitored for three consecutive cycles. During adulthood, anxiety and locomotor activity were assessed with an automated elevated plus maze (EPM) and automated activity monitors, respectively. After behavioral assessment, body weight, gonadal weight, and plasma levels of sex hormones were measured. Neonatal exposure to PREG-S produced anxiolytic effects in females but not males. The opposite effect was seen in males, suppression of locomotor behaviors without changes in anxiety. The day of vaginal opening, gonadal weight, and plasma levels of hormones in adult animals were not altered by neonatal treatment. We suggest that PREG-S exposure during neonatal development can have an impact in anxiety and locomotor behaviors during adulthood in a sex-specific manner.

The Testosterone Metabolite 3α‐Diol Enhances Female Rat Sexual Motivation When Infused in the Nucleus Accumbens Shell

AIM The purpose of this study was to provide a quantitative assessment of female rat sexual behaviors after acute exposure to the A-ring reduced testosterone metabolite, androstanediol (3α-Diol), through the nucleus accumbens (NA) shell. MAIN OUTCOME MEASURES Quantitative analyses of female rat sexual behaviors and assessment of protein levels for the enzyme glutamic acid decarboxylase isoform 67 (GAD67) and gephyrin, a protein that participates in the clustering of GABA-A receptors in postsynaptic cells, were accomplished. METHODS Female rats were ovariectomized and primed with estrogen and progesterone to induce sexual behaviors. Females received a 3α-Diol infusion via guided cannula that aimed to the NA shell five minutes prior to a sexual encounter with a stud male. The following parameters were videotaped and measured in a frame by frame analysis: lordosis quotient (LQ), Lordosis rating (LR), frequency and duration of proceptive behaviors (hopping/darting and ear wiggling). Levels of GAD67 and gephyrin were obtained by Western blot analysis two or twenty-four hours after the sexual encounter. RESULTS Acute exposure to 3α-Diol in the NA shell enhanced LR, ear wiggling, and hopping/darting but not LQ. Some of these behavioral effects were counteracted by co-infusion of 3α-Diol plus the GABAA-receptor antagonist GABAzine. A transient reduction of GAD67 levels in the NA shell was detected. CONCLUSIONS The testosterone metabolite 3α-Diol enhances sexual proceptivity, but not receptivity, when infused into the NA shell directly. The GABAergic system may participate in the androgen-mediated enhancement of female rat sexual motivation.

Central effects of the anabolic steroid 17α methyltestosterone in female anxiety

The androgen 17alpha-methyltestosterone (17alpha-meT) is one of the most commonly abused anabolic androgenic steroids (AAS). We assessed the impact of 17alpha-meT after bilateral infusion into the dorsomedial hypothalamus (DMH) in female anxiety. A paradoxical effect in Vogel conflict test (VCT) behavior was noted: while AAS infusion induced an increase in the latency to display the appetitive reaction of the task, it also increased the number of punished responses. No changes in elevated plus maze (EPM) behavior were noted. However, AAS infusion induced an increase in social interactions. Changes in social interactions were mimicked by muscimol infusion and counteracted by co-infusion of AAS plus the GABAA receptor (GABAA-R) antagonist GABAzine. A reduction of systolic blood pressure was registered after AAS infusion in the DMH. No changes in fluid intake or locomotor behaviors were noted. We conclude that the AAS 17alpha-meT modulates distinct anxiety domains in females through a fast-acting mechanism.

Steroid modulation of GABAA receptors:from molecular mechanisms to CNS roles in reproduction, dysfunction and drug abuse

Publisher Summary This chapter focuses on the steroid modulation of gamma-aminobutyric acid type A (GABA A ) receptors. Gamma-aminobutyric acid is the major inhibitory neurotransmitter in the adult mammalian CNS. This ubiquitous neurotransmitter binds to two structurally distinct classes of receptors: ion channel proteins, including the GABA A and GABA C receptors, and the G protein-coupled GABA B receptor. GABA A receptors are the members of the evolutionarily related superfamily of ligand-gated ion channels, including the nicotinic acetylcholine receptor and the glycine receptor families and the 5‑HT 3 subclass of receptors gated by serotonin. GABA A receptors are widely expressed throughout the vertebrate central nervous system (CNS) and subserve an essential role in mediating fast synaptic inhibitory transmission. Moreover, the GABA A receptor is the primary molecular target for a broad range of therapeutic and abused drugs, as well as a number of nervous system toxins. The chapter highlights the key aspects of GABA A receptor structure, function, and expression. It focuses on the way allosteric modulation of GABA A receptors by the derivatives of gonadal steroids regulates normal CNS processing, as well as the role it may play in specific disorders and in drug abuse.

Risk factors, prevalence trend, and clustering of hypospadias cases in Puerto Rico

OBJECTIVE The aim was to determine the distribution pattern of hypospadias cases across a well-defined geographic space. MATERIALS AND METHODS The dataset for this study was produced by the Birth Defects Prevention and Surveillance System of the Department of Health of Puerto Rico (BDSS-PR), which linked the information of male newborns of the Puerto Rico Birth Cohort dataset (PRBC; n=92,285) from 2007 to 2010. A population-based case-control study was conducted to determine prevalence trend and to estimate the potential effects of maternal age, paternal age, birth-related variables, and health insurance status on hypospadias. Two types of geographic information systems (GIS) methods (Anselin Local Morans I and Getis-Ord G) were used to determine the spatial distribution of hypospadias prevalence. RESULTS Birthweight (<2500 g), age of mother (40+years), and private health insurance were associated with hypospadias as confirmed with univariate and multivariate analyses at 95% CI. A cluster of hypospadias cases was detected in the north-central region of Puerto Rico with both GIS methods (p≤0.05). CONCLUSIONS The clustering of hypospadias prevalence provides an opportunity to assess the underlying causes of the condition and their relationships with geographical space.

Ultrasound Accuracy of Liver Length Measurement With Cadaveric Specimens

The liver is one of the principal organs in the body and is involved in over 500 physiological functions related to metabolism, digestion, immunity, and storage of nutrients. Given that there are a number of approaches to measure liver length through diagnostic 2D sonography, this work was undertaken to determine the most accurate measurement of this organ. Cadaveric specimens (n = 21) were employed to assess measurements in the midclavicular line (MCL) and the midaxillary line (MAL). Each measurement was calculated in anteroposterior (AP) and craniocaudal (CC) planes. In addition, in situ measurements were obtained by accessing the organ through the anterior thoracoabdominal wall. Statistical differences were detected between MCL and MAL measurements (P < .05), and a positive correlation between MAL CC and in situ anterior measurements were noted (r = 0.97). Liver size, as assessed through in situ measurements, varied as a funtion of BMI and waist circumference (P < .05). It is concluded that the craniocaudal measurement of the right lobe of the liver in the midaxillary line, from the uppermost right hemi-diaphragm to the inferior tip of the right lobe through a horizontal line parallel to the anterior liver wall, is the most accurate measurement of the organ by sonography.