Effect of methylphenidate treatment during adolescence on norepinephrine transporter function in orbitofrontal cortex in a rat model of attention deficit hyperactivity disorder

Attention deficit hyperactivity disorder (ADHD) is associated with hypofunctional medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC). Methylphenidate (MPH) remediates ADHD, in part, by inhibiting the norepinephrine transporter (NET). MPH also reduces ADHD-like symptoms in spontaneously hypertensive rats (SHRs), a model of ADHD. However, effects of chronic MPH treatment on NET function in mPFC and OFC in SHR have not been reported. In the current study, long-term effects of repeated treatment with a therapeutically relevant oral dose of MPH during adolescence on NET function in subregions of mPFC (cingulate gyrus, prelimbic cortex and infralimbic cortex) and in the OFC of adult SHR, Wistar-Kyoto (WKY, inbred control) and Wistar (WIS, outbred control) rats were determined using in vivo voltammetry. Following local ejection of norepinephrine (NE), uptake rate was determined as peak amplitude (Amax)× first-order rate constant (k-1). In mPFC subregions, no strain or treatment effects were found in NE uptake rate. In OFC, NE uptake rate in vehicle-treated adult SHR was greater than in adult WKY and WIS administered vehicle. MPH treatment during adolescence normalized NE uptake rate in OFC in SHR. Thus, the current study implicates increased NET function in OFC as an underlying mechanism for reduced noradrenergic transmission in OFC, and consequently, the behavioral deficits associated with ADHD. MPH treatment during adolescence normalized NET function in OFC in adulthood, suggesting that the therapeutic action of MPH persists long after treatment cessation and may contribute to lasting reductions in deficits associated with ADHD.UL1 TR000117 - NCATS NIH HHS; R01 DA011716 - NIDA NIH HHS; P50 DA005312 - NIDA NIH HHS; P50 DA05312 - NIDA NIH HHS; R01 DA11716 - NIDA NIH HH

Effect of methylphenidate treatment during adolescence on norepinephrine transporter function in orbitofrontal cortex in a rat model of attention deficit hyperactivity disorder

Attention deficit hyperactivity disorder (ADHD) is associated with hypofunctional medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC). Methylphenidate (MPH) remediates ADHD, in part, by inhibiting the norepinephrine transporter (NET). MPH also reduces ADHD-like symptoms in spontaneously hypertensive rats (SHRs), a model of ADHD. However, effects of chronic MPH treatment on NET function in mPFC and OFC in SHR have not been reported. In the current study, long-term effects of repeated treatment with a therapeutically relevant oral dose of MPH during adolescence on NET function in subregions of mPFC (cingulate gyrus, prelimbic cortex and infralimbic cortex) and in the OFC of adult SHR, Wistar-Kyoto (WKY, inbred control) and Wistar (WIS, outbred control) rats were determined using in vivo voltammetry. Following local ejection of norepinephrine (NE), uptake rate was determined as peak amplitude (Amax)× first-order rate constant (k-1). In mPFC subregions, no strain or treatment effects were found in NE uptake rate. In OFC, NE uptake rate in vehicle-treated adult SHR was greater than in adult WKY and WIS administered vehicle. MPH treatment during adolescence normalized NE uptake rate in OFC in SHR. Thus, the current study implicates increased NET function in OFC as an underlying mechanism for reduced noradrenergic transmission in OFC, and consequently, the behavioral deficits associated with ADHD. MPH treatment during adolescence normalized NET function in OFC in adulthood, suggesting that the therapeutic action of MPH persists long after treatment cessation and may contribute to lasting reductions in deficits associated with ADHD.UL1 TR000117 - NCATS NIH HHS; R01 DA011716 - NIDA NIH HHS; P50 DA005312 - NIDA NIH HHS; P50 DA05312 - NIDA NIH HHS; R01 DA11716 - NIDA NIH HH

METHYLPHENIDATE AND ATOMOXETINE TREATMENT DURING ADOLESCENCE IN THE SPONTANEOUSLY HYPERTENSIVE RAT: MECHANISMS UNDERLYING HIGH COCAINE ABUSE LIABILITY IN ATTENTION DEFICIT/HYPERACTIVITY DISORDER

Effects of pharmacotherapies for Attention Deficit/Hyperactivity Disorder (ADHD) on cocaine abuse liability in ADHD are not understood. Spontaneously Hypertensive Rats (SHR), an ADHD model, exhibited greater cocaine self-administration than control Wistar-Kyoto and Wistar rats. Methylphenidate, but not atomoxetine during adolescence enhanced cocaine self-administration in adult SHRs compared to controls. The mesocortical dopaminergic system, including medial prefrontal (mPFC) and orbitofrontal (OFC) cortices, is important for ADHD and cocaine addiction. Dopamine and norepinephrine transporter (DAT and NET) are molecular targets for methylphenidate, atomoxetine and cocaine action. In the current studies, SHR, Wistar-Kyoto and Wistar were administered methylphenidate (1.5 mg/kg/day, p.o.), atomoxetine (0.3 mg/kg/day, i.p.) or vehicle during adolescence (postnatal day 28-55). During adulthood (\u3e77 days), DAT and NET functions in mPFC and OFC were determined as neurochemical mechanisms and locomotor sensitization to cocaine, and impulsivity under differential reinforcement of low rates 30-second (DRL30) schedule were evaluated as behavioral mechanisms associated with greater cocaine self-administration in methylphenidate-treated SHRs. Maximal velocity of [3H]dopamine uptake (Vmax) by DAT and DAT cellular distribution in mPFC and OFC did not differ between vehicle-control, adult SHR, Wistar-Kyoto and Wistar. Methylphenidate increased DAT Vmax, but not cell-surface expression, in SHR mPFC. In contrast, atomoxetine decreased Vmax and cell-surface expression in SHR OFC. Compared to control strains, norepinephrine uptake by NET in the OFC was increased in vehicle-administered SHR; methylphenidate during adolescence normalized NET function in SHR OFC. Locomotor sensitization was greater in SHR compared to control, and was not altered by methylphenidate. Under DRL30, methylphenidate increased burst responses in adult SHR compared to vehicle control as well as methylphenidate-treated Wistar-Kyoto and Wistar, indicating increased impulsivity. Increased OFC NET function, increased impulsivity and cocaine sensitivity may be the neurobehavioral mechanisms associated with the increased cocaine self-administration in SHR. Increased mPFC DAT function may underlie the enhanced impulsivity and cocaine self-administration in SHR administered methylphenidate during adolescence. Decreased OFC DAT function from atomoxetine-treated SHR may explain the reduced cocaine self-administration relative to methylphenidate. Thus, methylphenidate during adolescence in ADHD may increase risk for cocaine abuse, while atomoxetine may represent a therapeutic alternative for at-risk adolescents with ADHD

Adolescent methylphenidate treatment differentially alters adult impulsivity and hyperactivity in the Spontaneously Hypertensive Rat model of ADHD

Impulsivity and hyperactivity are two facets of attention deficit/hyperactivity disorder (ADHD). Impulsivity is expressed as reduced response inhibition capacity, an executive control mechanism that prevents premature execution of an intermittently reinforced behavior. During methylphenidate treatment, impulsivity and hyperactivity are decreased in adolescents with ADHD, but there is little information concerning levels of impulsivity and hyperactivity in adulthood after adolescent methylphenidate treatment is discontinued. The current study evaluated impulsivity, hyperactivity as well as cocaine sensitization during adulthood after adolescent methylphenidate treatment was discontinued in the Spontaneously Hypertensive Rat (SHR) model of ADHD. Treatments consisted of oral methylphenidate (1.5mg/kg) or water vehicle provided Monday-Friday from postnatal days 28-55. During adulthood, impulsivity was measured in SHR and control strains (Wistar Kyoto and Wistar rats) using differential reinforcement of low rate (DRL) schedules. Locomotor activity and cocaine sensitization were measured using the open-field assay. Adult SHR exhibited decreased efficiency of reinforcement under the DRL30 schedule and greater levels of locomotor activity and cocaine sensitization compared to control strains. Compared to vehicle, methylphenidate treatment during adolescence reduced hyperactivity in adult SHR, maintained the lower efficiency of reinforcement, and increased burst responding under DRL30. Cocaine sensitization was not altered following adolescent methylphenidate in adult SHR. In conclusion, adolescent treatment with methylphenidate followed by discontinuation in adulthood had a positive benefit by reducing hyperactivity in adult SHR rats; however, increased burst responding under DRL compared to SHR given vehicle, i.e., elevated impulsivity, constituted an adverse consequence associated with increased risk for cocaine abuse liability.P50 DA005312 - NIDA NIH HHS; R01 DA011716 - NIDA NIH HHS; P50 DA05312 - NIDA NIH HH

Effect of Leaf Removal on Composition of Wine Grape Varieties Grown in Semiarid Tropical Climate of India

Removing leaves from cluster zone is one of the management practices followed to improve fruit composition in temperate wine grape growing countries. However, knowledge on canopy management practices to improve fruit and juice composition for quality wine making is still lacking in semiarid tropical regions of India. Due to ample sunlight availability during fruit growth in semiarid tropics, it is unclear whether the leaves have to be removed from cluster zone. In case the leaves have to be removed, the direction from which it has to be done is also important. Hence, this study was conducted to see the effect of leaf removal from two sides of canopy on fruit composition in two wine grape varieties. In Cabernet Sauvignon vines leaf removal from both east and west side of the canopyimproved fruit quality in terms of reduced pH, potassium, malic acid and increased phenolics. Nevertheless, removing leaves from eastern side was found to be better than western side, because clusters are exposed toexcess sunlight. However, in Sauvignon Blanc, leaf removal from east side improved most of the desirable fruit composition parameters, while leaf removal from west side reduced the fruit quality in terms of sugars, acids, pH, total phenols etc

Isolated congenital factor VII deficiency

Congenital factor VII (FVII) (proconvertin) is a rare autosomal recessive bleeding disorder. Bleeding manifestations and clinical findings vary widely, ranging from being asymptomatic to life-threatening bleeding. Intracranial bleeding is relatively less common with inherited FVII deficiency than with other coagulation disorders. We report a rare case of congenital FVII deficiency in an 11-year-old male child. The patient had recurrent subdural hemorrhages. The prothrombin time was markedly prolonged with a normal bleeding time, normal partial thromboplastin time and normal platelet count. Treatment consists of replacement therapy with fresh frozen plasma, prothrombin complex concentrates or plasma-derived FVII concentrates, and/or recombinant factor VIIa. Clinical heterogeneity is the hallmark of this disorder

Floyd-Warshall Algorithm 1

Abstract: There are several applications in VLSI technology that require high-speed shortest-path computations. The shortest path is a path between two nodes (or points) in a graph such that the sum of the weights of its constituent edges is minimum. Floyd-Warshall algorithm provides fastest computation of shortest path between all pair of nodes present in the graph. With rapid advances in VLSI technology, Field Programmable Gate Arrays (FPGAs) are receiving the attention of the Parallel and High Performance Computing community. This paper gives implementation outcome of Floyd-Warshall algorithm to solve the all pairs shortest-paths problem for directed graph in Verilog

Design And Implementation Of Electrical Transmission Line Monitoring And Controlling System

As the electric transmission line is spread widely at long distance location is become difficult to monitor, control the power supply in the transmission line. Physical inspection at every location and troubleshooting is not feasible. Same problem is still facing at traffic monitor and control units as every square which are currently controlled manually by operator. Wireless Sensor Network (WSN) provides access over remote location with centralized monitoring and controlling on different channels so it can be utilized for electric transmission line monitoring. While the WSNs are capable of cost efficient monitoring over vast geo-locations, several technical challenges exist. To overcome these problems in regional areas proposed system is designed to monitor and control the electric transmission line using WSN. Here we are building a wireless node which can centrally monitor and controlled through base station or the wireless cluster head. A centralized server will be responsible to see the electric poll status and control the poll activities to enable or disable power in particular area. As it is not feasible to monitor the central server full time, So the proposed system is designed to have emergency alert system for remote user with the help of a GSM modem will be connected to the central server which will send the emergency alert SMS to administrator and user. DOI: 10.17762/ijritcc2321-8169.150712