Co-administration of bromocriptine and corticosterone produces short- and long-lasting reduction in intake of high-fat food in male rats.

Dopaminergic and glucocorticoid activity has been associated with reduced food consumption; however, their possible synergic action has not yet been studied. With the aim of examining the effect of the co-administration of the dopamine receptor D2 agonist bromocriptine and corticosterone on palatable food intake, male Wistar rats were administered either bromocriptine (1 mg/kg), corticosterone (2 mg/kg), bromocriptine + corticosterone (1 mg + 2 mg/kg) or a vehicle, with a fifth group used as a control. In all cases, substances were administered 30 min before exposure to standard food or palatable food, the latter high in carbohydrates [high carbohydrate food (HCF), 75%] or high-fat food (HFF, 67%). Food consumption and body weight were recorded daily. Results showed higher consumption of standard food but lower consumption of HCF and HFF in the groups that received bromocriptine, alone or in combination. In general, lower total kcal intake was observed in the bromocriptine and bromocriptine + corticosterone groups during the period of pharmacological treatment and following re-exposure to palatable food. The low HFF intake in the bromocriptine + corticosterone group persisted 10 days after the pharmacological treatment was interrupted. This effect suggests plastic changes in either the mechanisms involved in the incentive value of palatable food - particularly foods with high-fat content - or those that regulate lipid metabolism. Our findings suggest that homeostatic and reward mechanisms could be influenced by the co-participation of the dopaminergic and hypothalamic-pituitary-adrenal systems, and the macronutrient content of food.

Chiral Indolizinium Salts Derived from 2-Pyridinecarbaldehyde-First Diastereoselective Syntheses of (-)-1-epi-lentiginosine.

The first diastereoselective synthesis of (-)-1-epi-lentiginosine from a common chiral trans-epoxyamide derived from 2-pyridincarbaldehyde is reported. This methodology involves a sequential oxirane ring opening and intramolecular 5-exo-tet cyclization of tosylate trans-epoxyalcohol to afford a diastereomeric mixture of indolizinium salts in a one-pot fashion, followed by regio- and diastereospecific pyridinium ring reduction.

Tai Chi as a Complementary Therapy for Depression and Anxiety Among U.S. Veterans in a Mental Health Inpatient Setting.

BACKGROUND: Depression and anxiety are two of the top five mental illnesses veterans report. Treatment for depression and anxiety includes medications and psychiatric treatment in inpatient, outpatient, and residential treatment programs; the use of complementary and alternative medicine (CAM) can have beneficial results by decreasing symptoms, recognize patients' preference for CAM, and be cost-effective. AIM: This study aimed to evaluate the effects of Tai Chi on depression and anxiety symptoms on inpatient psychosocial or substance use disorder (SUD) rehabilitation treatment program residents since little evidence exists regarding the effectiveness of Tai Chi on participants in residential mental health treatment programs. METHOD: A mixed-method, cohort design with 88 participants (41 usual treatment without Tai Chi, 47 intervention) used a demographic survey, Hamilton Anxiety Scale, Quick Inventory of Depressive Symptomatology, self-report, and the Patient Health Questionnaire-9 at Weeks 1 and 4 of the treatment program. After Week 4, the intervention group responded to six open-ended questions about Tai Chi's effects on their overall depression and anxiety. RESULTS: The anxiety level of the intervention group was significantly decreased, as evidenced by the Hamilton Anxiety Scale scores (p = .02). However, the measures of depression did not differ between the groups. Two themes, mindfulness and satisfaction, were identified from the written responses regarding the Tai Chi intervention. CONCLUSION: Tai Chi effectively reduced symptoms of anxiety that varied by age and ethnicity. This study increased the insight regarding the benefit of including Tai Chi as a complementary therapy for those participating in residential treatment programs.

Differential effects of citalopram on the intake of high fat or high carbohydrates diets in female and male rats.

Chronic administration of selective serotonin reuptake inhibitors (SSRI), usually prescribed as antidepressants, decreases total energy intake; however, at present the differential effect on the intake of distinct macronutrients and on female vs. male organisms is not clear. On this basis, female and male adult Wistar rats were exposed to two types of diets: (1) a standard balanced diet (BD); or (2) two types of diets simultaneously, (a) one high in carbohydrates (HC); the other (b) high in fat (HF). Both study groups were given a dose of 10 mg/kg/day i.p. of citalopram or a vehicle for 21 days. Food and water consumption and body weight were recorded daily at baseline (BL), during treatment (TX), and post-treatment (PTx1-PTx2). The male rats exposed to BD reduced total energy consumption during treatment with citalopram, but body weight gain decreased both females and males compared to BL. During exposure to the two types of diets, citalopram treatment reduced fat consumption with respect to BL and PTx1 only in the male group. This group also decreased its total energy consumption during TX compared to PTx1. Finally, the females gained less body weight in TX than PTx1, while weight gain in the males during TX decreased with respect to BL and PTx1. Results show a differential effect of citalopram on females vs. males that was dependent on the type of macronutrient administered.

Chronic early-life stress increases cognitive impulsivity and D2 immunoreactivity in the nucleus accumbens of adult rats.

Chronic early life stress (ECS) induced by limited bedding and nesting (LBN) material in rodents is a naturalistic stress model that mimics many of the behavioral and neural consequences of child abuse and neglect; however, the effect of ECS on adult impulsivity has never been studied. The aim of our work was to determine the effects of ECS on cognitive impulsivity and its relation to D2 immunoreactivity in the nucleus accumbens (NAc) and prefrontal cortex (PFC) of adult male rats. Sprague-Dawley rats were exposed to LBN from postnatal day 2 to 9. We evaluated dams' maternal behavior and offspring corticosterone levels. The rats' impulsive cognitive behavior was evaluated by a delay-discounting task (transitional bridge) on P70, and we evaluated D2 receptors by immunostaining. Our results indicated that ECS affected maternal behavior in the dams and increased pups' corticosterone levels at P9, but not in adults. ECS rats showed lower frequencies of choosing the delayed reinforcer and shorter latencies to cross on the delay-discounting task. In addition, ECS rats showed increased D2 immunoreactivity in the NAc when compared with controls. Our data suggest that ECS can cause impulsive behaviors in adult rats characterized by less convenient choices, likely related to an increase in D2 receptors in the NAc. These findings could contribute to our understanding of the effects of child abuse and neglect on impulsive behavior.

Impact of embryo technologies on secondary sex ratio in rabbit.

Increasing evidence indicates that assisted reproductive technologies (ARTs) disturb skewed sex-ratio and induce sex-dimorphic postnatal effects. Undoubtedly, the combination of multiple ovulation and embryo transfer (MOET) together with the use of vitrification technique (MOVET) is currently being used in breeding programs. However, since the first case of sex skewing reported in 1991, the accumulative and long-term transmission of skewed sex-ratio to future generations has not been thoroughly evaluated. Here we test as MOVET program induce a skewed sex ratio, and we consider skewed sex ratio transmission to future generations. To this end, we first evaluated the F1 generation, demonstrating that a MOVET program causes a severe imbalance skewed secondary sex ratio (SSR) towards male by 12%. This imbalanced persist after a second MOVET program (F2 generation), with an accumulative skewed SSR towards male by 25%. Finally, using a crossbred generation derived from crossing F1 males derived from a MOVET program with naturally-conceived (NC) females, we show that the imbalance skewed SRR persist. Bodyweight comparison between MOVET animals and NC counterparts revealed significant changes at birth, weaning and adulthood. However, there was a significant interaction between F2 MOVET animals and sex, demonstrating an apparent accumulative sex-dimorphic effect. At adulthood, MOVET derived males presented a lower body weight. In conclusion, we show that the MOVET program causes a direct, accumulative and long-term transmission of skewed SSR.

Changes in the incentive value of food after naltrexone treatment depend on a differential preference for a palatable food in male rats.

INTRODUCTION: Opioid antagonist treatments such as naltrexone (NTX) and naloxone reduce consummatory behavior of palatable food (PF) and other incentives. Meanwhile, a significant increase in alcohol consumption has been observed when it is offered immediately after ending NTX treatment, an effect apparently produced by increased opioidergic activity caused by up-regulation of opioid receptors. OBJECTIVE: On this basis we assessed changes in the consumption of PF after opioid antagonist treatment in rats with different preferences for that food. METHODS: The preference of male Wistar rats for a PF was classified as low, medium, or high in a baseline period, after which the animals in each preference level were sub-divided into control and experimental groups that received injections of either NTX (2 mg/kg twice per day/6 days) or a saline solution with a space of 8 hours between doses. At the end of pharmacological treatment (PT), subjects were re-exposed to the PF. RESULTS: Increased PF intake was found only in the low-preference group, but the increase was observed in both the experimental and control animals. Also, a decrease in chow intake during PT was observed in all preference groups, while recovery after treatment was noted only in the low-preference rats. DISCUSSION: The increased intake observed in the low-preference rats after treatment phase suggests that the hypothalamic-pituitary-adrenal axis activation during PT could have enhanced the rewarding characteristics of the sweet food and so facilitated and increased its consumption in the re-exposure period.

Differential Improvement of Executive Functions During Abstinence in Cocaine-Dependent Patients: A Longitudinal Study.

BACKGROUND: In substance abusers, deficits in executive functioning (EF) are relevant to understanding the behavioral regulation of substance consumption and the failure to remain abstinent. OBJECTIVE: To determine the course of EF impairment, measured with traditional and ecological instruments, after 1 and 3 months of abstinence in patients with cocaine dependence. METHODS: 26 cocaine-only-dependent in-patients (cocaine-dependent group, CDG) and 24 nondependent controls (control group, CG) recruited from a typical population were assessed using several EF tests and questionnaires [Stroop, verbal and graphic fluency, Wisconsin Card-Sorting Test (WCST), Tower of London (TOL), and Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A)] after three periods of abstinence: 1 week, 1 month, and 3 months. RESULTS: At 1 week (baseline), CDG underperformed CG on most EF measures (WCST categories completed; TOL-total number of moves, execution time, and rule violations; and various BRIEF-A subscales). At 1 month, CDG moderately improved its performance on several measures, meanwhile the improvement in the 12 patients who would eventually complete the 3-month abstinence proved particularly significant when compared to their baseline values. In the a posteriori comparison of the baseline values of noncompleters versus completers, scores for the former were lower on the EF tasks, but higher on the BRIEF-A. Both groups, showed significantly worse scores than CG on both instruments. CONCLUSIONS/IMPORTANCE: Cocaine-dependent patients showed marked difficulties in the EF associated mainly with adaptive behavior to their environment. Cocaine-dependent patients with better EF at baseline improved significantly during abstinence and had better treatment adherence. Results suggest that executive improvement and treatment adherence in cocaine abusers in abstinence is related to intrinsic cognitive characteristics of patients.

Atomoxetine promotes incentive value of modafinil and sensitizes exploratory behavior.

Substance dependence is a disorder that alters the functioning of the nervous system due to frequent abuse of drugs. The role of dopamine in the addictive effect of psychostimulants is well known; however, the involvement of the noradrenergic system is still unclear and poorly understood, though drugs like cocaine and amphetamines are known to exert significant activity on this system. The drug modafinil (MOD) has no proven addictive effect. It promotes wakefulness by acting mainly on the dopaminergic system and, to a lesser degree, the noradrenergic (NOR) system. Atomoxetine (ATX) is a non-stimulant drug that acts only on the NOR system, enhancing its activity. The aims of the present study were to analyze the effect of co-activating the DA and NOR systems (with MOD and ATX, respectively) on motor activity and exploratory behavior, and to examine the possible emergence of rewarding properties of MOD and an MOD+ATX mixture. Male Wistar rats at postnatal day 60 were treated chronically (16 days) with either monotherapy with 2ATX, 4ATX, or 60MOD mg/kg, two combinations of these substances -60MOD + 2ATX and 60MOD + 4ATX- or a vehicle. The rats co-administered with 60MOD + 4ATX reduced the rearing behavior frequency induced by MOD, but this behavior was sensitized by self-administration of the MOD+ATX mixture after chronic treatment. The rats pre-treated with 60MOD + 4ATX showed higher self-administration of MOD and greater activity on an operant task to obtain the MOD+ATX mixture. In addition, the 60MOD, 2ATX, and 60MOD + 2ATX groups showed sensitization of exploratory behavior after ingesting the mixture. Results suggest that the noradrenergic system enhances the incentive value of MOD and a MOD+ATX mixture, while also playing an important role in the sensitization of exploratory behavior.

Cortisol modulates Ca2+ signaling and acrosome reaction in human sperm.

BACKGROUND: Stress and elevated cortisol levels have negative effects on fertility, although there is controversy about the effect of cortisol on human sperm. One study reported that hydrocortisone (HC), the synthetic form of cortisol, does not activate CatSper channel but is able to inhibit its activation by progesterone (Pg). However, subsequent reports showed that HC has an agonist effect on CatSper, producing intracellular Ca2+ ([Ca2+ ]i ) increases. These studies were performed using only electrophysiological techniques and fluorometric measurements of Ca2+ . Therefore, it is important to evaluate the effects of different HC concentrations on human sperm physiology using other approaches and techniques. OBJECTIVE: To analyze the effects of different HC concentrations on human sperm physiology and to evaluate the association of perceived stress, anxiety and depression with acrosome reaction (AR), and semen quality. MATERIALS AND METHODS: In capacitated human sperm, we tested the effects of HC on [Ca2+ ]i mobilization and AR. Furthermore, the perceived stress and symptoms of anxiety and depression were evaluated with standardized psychometric tests. RESULTS: HC induces a low increase in [Ca2+ ]i compared to Pg response while, at higher concentrations, HC inhibits the Pg-induced Ca2+ response. Also, low concentrations of HC induce AR and when co-incubating it with Pg, the percentages of AR are decreased. Finally, the anxiety symptoms are negatively correlated with Pg induced AR and semen quality. DISCUSSION: HC has an agonist effect on [Ca2+ ]i mobilization and AR. However, our data also suggest that HC may compete for the binding site of Pg. Additionally, the association between anxiety and decreased AR could be explained by high cortisol levels. CONCLUSION: Our data showed that HC interferes with the Pg action. Therefore, the negative correlation between anxiety symptoms and Pg-induced AR is due to the accompanying high cortisol levels of this condition and its competitive action with Pg.

(S)-(-)-2-(1H-Indol-3-yl)-N-(1-phenyl-eth-yl)acetamide.

In the title compound, C(18)H(18)N(2)O, the dihedral angle between the indole system and the phenyl ring is 17.2 (2)°. The crystal packing features two N-H⋯O hydrogen bonds, which link the mol-ecules into layers parallel to (001). The absolute configuration was determined by the synthetic procedure and was set according to the starting material.

(R)-3,3-Diethyl-1-(2-hy-droxy-1-phenyl-eth-yl)piperidin-2-one.

In the title compound C(17)H(25)NO(2), the piperidin-2-one ring adopts an envelope conformation with the C atom in the 5-position as the flap. The crystal packing is stabilized by inter-molecular O-H⋯O hydrogen bonds, building a infinite chain along the b-axis direction. C-H⋯π inter-actions further stabilize the crystal packing.

(7aS)-(-)-Dimeth-yl(1-oxido-3-oxo-5,6,7,7a-tetra-hydro-3H-pyrrolizin-2-yl)sulfonium.

In the zwitterionic title compound, C(9)H(13)NO(2)S, the pyrrolidine heterocycle adopts an envelope conformation (with the C atom in the 7-position as the flap). The negative charge is delocalized over the two carbonyl groups and the C atom connecting them. The positive charge is located on the S atom. Two inter-molecular C-H⋯O inter-actions are observed. The molecular geometry at the S atom is trigonal pyramidal.

Modafinil acquires reinforcing effects when combined with citalopram.

Modafinil (MOD) is a wakefulness promoter used to treat sleep disorders such as narcolepsy and obstructive sleep apnea. Its action mechanism consists in inhibiting dopamine (DAT) and norepinephrine (NET) transporters, but it has no affinity for the serotonin transporter (SERT). Modafinil's addictive potential is not yet clear, but one feature that differentiates it from potentially addictive drugs like cocaine revolves around affinity for SERT. The aims of the present study were to determine whether co-administration of MOD with the selective serotonin reuptake inhibitor citalopram (CIT) can increase MOD's psychostimulant effects on motor activity (MA), verify the effects of subsequent self-administration of MOD mixed with CIT, and document the presence of any symptoms of withdrawal. At 60 postnatal days (PD), male Wistar rats were treated chronically (16 days) with MOD at 30 or 60 mg/kg, with MOD+CIT at four dosage combinations administered to four groups (30MOD + CIT3, 30MOD + CIT5, 60MOD + CIT3, 60MOD + CIT5 mg/kg), or with a vehicle. After 40 min of daily drug administration, MA was measured on the open field test. MA increased only in the 60MOD group. The rats co-administered with 30MOD + 3CIT and 60MOD + 3CIT showed a decrease in the motivation to seek a pleasurable stimulus (lower consumption of sweet solution) after treatment concluded. The 60MOD and 60MOD + 3CIT groups showed MA sensitization after MOD intake. Additionally, higher self-administration of the mixture was observed in the groups pre-treated with 30MOD + 3CIT and 60MOD + 3CIT. Results suggest that serotonergic activity enhances modafinil's psychostimulant effects.

Diastereoselective synthesis of new zwitterionic bicyclic lactams, scaffolds for construction of 2-substituted-4-hydroxy piperidine and its pipecolic acid derivatives.

The synthesis of new chiral highly functionalized zwitterionic bicyclic lactams starting from acyclic ß-enaminoesters derived from (R)-(-)-2-phenylglycinol is described. The key step involved an intramolecular non-classical Corey-Chaykovsky ring-closing reaction of the corresponding sulfonium salts derived from ß-enaminoesters. This methodology permits the generation of two or three new stereogenic centers with high diastereoselectivity. The utility of these intermediates was demonstrated by the stereocontrolled total synthesis of cis-4-hydroxy-2-methyl piperidine and its corresponding pipecolic acid derivative.

Observation of speckle pattern formation in transparent nonlinear random media.

We report on the experimental observation of speckle formation from a transparent crystal formed by a random distribution of nonlinear domains. The angular distribution of second-harmonic light generated by a transparent strontium barium niobate crystal is measured for different diameters of the fundamental beam and crystal thicknesses. Distinct manifestations of speckle pattern formation are found in these experiments. By using a theoretical Green's function formalism, we explain the reported observations as a result of the linear interference among the second-harmonic waves generated in all directions by each of the nonlinear domains forming the nonlinear crystal.

Boar semen can tolerate rapid cooling rates prior to freezing.

Two experiments were performed in the present study that demonstrated that boar spermatozoa are capable of surviving rapid cooling rates within a range of 15-5 °C before freezing. Boar ejaculates diluted in Beltsville thawing solution (BTS) (1:1, v/v) were held at 17-20 °C and shipped over a 24-h time period from two AI centres to a cryobiology laboratory, where they were pooled (Experiment 1) or cryopreserved individually (Experiment 2) using a standard 0.5-mL straw freezing protocol. The effects of cooling before freezing were assessed after thawing through the objective evaluation of sperm motility and flow cytometric analysis of membrane integrity, acrosomal status, changes in membrane lipid architecture monitored by merocyanine and annexin V binding and intracellular production of reactive oxygen species. In Experiment 1 (six replicates), two semen pools (five ejaculates per pool) were cooled from 15 to 5 °C at rates of 0.08, 0.13, 0.40 and 1.50 °C min(-1). These cooling rates did not result in any significant differences (P>0.05) in any of the post-thaw sperm assessments, even in thawed samples incubated under capacitation conditions. In Experiment 2, three individual ejaculates from 16 boars were slowly (0.08 °C min(-1)) or rapidly (1.5 °C min(-1)) cooled before freezing. A consistent interboar variability (P<0.01) was detected, which was independent of the cooling rate used. Cooling rate only significantly influenced (P<0.05) sperm assessments in four of 16 boars, which exhibited slightly higher percentages of motile cells and intact plasma and acrosomal membranes in the samples that had been cooled slowly. These findings demonstrate that boar spermatozoa undergoing cryopreservation can withstand rapid cooling rates before freezing.

(R)-(+)-Dimeth-yl[4-oxido-2-oxo-1-(1-phenyl-eth-yl)-1,2,5,6-tetra-hydro-pyridin-3-yl]sulfonium.

In the title zwitterionic compound, C(15)H(19)NO(2)S, the six-membered heterocycle adopts a sofa conformation. The negative charge is delocalized along the carbonyl and enolate system on the ring and the positive charge is localized on the S atom. Two inter-molecular C-H⋯O inter-actions help to establish the packing.

Microfabrication with Very Low-Average Power of Green Light to Produce PDMS Microchips.

In this article, we show an alternative low-cost fabrication method to obtain poly(dimethyl siloxane) (PDMS) microfluidic devices. The proposed method allows the inscription of micron resolution channels on polystyrene (PS) surfaces, used as a mold for the wanted microchip's production, by applying a high absorption coating film on the PS surface to ablate it with a focused low-power visible laser. The method allows for obtaining micro-resolution channels at powers between 2 and 10 mW and can realize any two-dimensional polymeric devices. The effect of the main processing parameters on the channel's geometry is presented.

Optical second-harmonic scattering from a non-diffusive random distribution of nonlinear domains.

We show that the weak second harmonic light generated from a random distribution of nonlinear domains of transparent Strontium Barium Niobate crystals can display a particularly intense generation in the forward direction. By using a theoretical model able to analyze the optical response of arbitrary distributions of three-dimensional nonlinear volumes of any shape, we found that the physical origin of this observation can be explained in terms of the scattering of light by a single nonlinear domain.