Rationale-Corticotropin releasing factor (CRF) produces anxiety-like and aversive effects when infused directly into the various regions of the brain, including the bed nucleus of the stria terminalis (BNST). However, the CRF receptor subtypes within the BNST mediating these phenomena have not been established.Objectives-We used selective CRF receptor antagonists to determine the receptor subtypes involved in the anxiogenic-like and aversive effects CRF in the BNST. Methods-MaleLong-Evans rats were bilaterally infused with CRF (0.2 or 1.0 nmol) either alone or in combination with the CRF 1 receptor antagonist CP154,526 or the CRF 2 receptor antagonist anti-sauvagine 30 (AS30) prior to behavioral testing in the elevated plus maze or place conditioning paradigms.Results-Intra-BNST administration of CRF produced a dose-dependent reduction in open arm entries and open arm time in the elevated plus maze, indicating an anxiogenic-like effect. These effects were inhibited by co-infusion of CP154,526 but not AS30, indicating that the anxiogeniclike effects of CRF in the BNST are mediated by CRF 1 receptors. Place conditioning with intra-BNST administration of CRF produced a dose-dependent aversion to the CRF-paired environment that was prevented by co-infusion of either CP154,526 or AS30, indicating that both CRF receptor subtypes mediate the aversive effects of this peptide. Intra-BNST infusions of the CRF receptor antagonists alone produced no effects in either behavioral paradigm.Conclusions-CRF 1 receptors in the BNST mediate the anxiogenic-like effects CRF in this region, whereas both CRF 1 and CRF 2 receptor subtypes mediate the conditioned aversive effects of this peptide within the BNST.

Glutamatergic neurotransmission plays a critical role in addictive behaviors, and recent evidence indicates that genetic or pharmacological inactivation of the type 5 metabotropic glutamate receptor (mGluR5) reduces the self-administration of cocaine, nicotine, and alcohol. Because mGluR5 is coupled to activation of protein kinase C (PKC), and targeted deletion of the epsilon isoform (PKC⑀) in mice reduces ethanol self-administration, we investigated whether there is a functional link between mGluR5 and PKC⑀. Here, we show that acute administration of the mGluR5 agonist (R,S)-2-chloro-5-hydroxyphenylglycine to mice increases phosphorylation of PKC⑀ in its activation loop (T566) as well as in its C-terminal region (S729). Increases in phospho-PKC⑀ are dependent not only on mGluR5 stimulation but also on phosphatidylinositol-3 kinase (PI3K). In addition, the selective mGluR5 antagonist 6-methyl-2-(phenylethynyl)pyridine (MPEP) reduced basal levels of phosphorylation of PKC⑀ at S729. We also show that MPEP dose dependently reduced ethanol consumption in wild-type but not in PKC⑀-null mice, suggesting that PKC⑀ is an important signaling target for modulation of ethanol consumption by mGluR5 antagonists. Radioligand binding experiments using [3 H]MPEP revealed that these genotypic differences in response to MPEP were not a result of altered mGluR5 levels or binding in PKC⑀-null mice. Our data indicate that mGluR5 is coupled to PKC⑀ via a PI3K-dependent pathway and that PKC⑀ is required for the ability of the mGluR5 antagonist MPEP to reduce ethanol consumption.Glutamatergic neurotransmission plays an important role in the behavioral and neurochemical effects of drugs of abuse as well as in drug self-administration. Although most studies have examined the role of ionotropic glutamate receptor subtypes (Tzschentke and Schmidt, 2003;Kalivas, 2004), there is increasing evidence that metabotropic glutamate receptors (mGluRs) also play an important role in drug-related behaviors (Kenny and Markou, 2004;Olive, 2005). For example, mice lacking the type 5 mGluR (mGluR5) show dramatically reduced levels of cocaine self-administration and cocaineinduced hyperactivity (Chiamulera et al., 2001). In addition, studies using selective mGluR5 antagonists have confirmed a role for mGluR5 in cocaine-related behaviors such as conditioned place preference (Mcgeehan and Olive,

This study compared measures of sleep from an accelerometer worn on the hip to measures obtained from an accelerometer worn on the wrist, the gold standard measure of sleep behavior in community research. The accelerometer worn on the hip provides a measure of TST in 10-11 year old children comparable to the wrist-worn unit. We provide an alternate method to ascertain bedtime and final wake time when diary data are missing. A hip-worn accelerometer may provide a cost-effective means of gathering physical activity and sleep data simultaneously in large samples of children with or without an accompanying sleep diary.

Background The after-school period is an important potential venue for increasing youths’ physical activity levels. We sought to assess the effectiveness of the Sports, Play, and Recreation for Youth (SPARK) program to increase physical activity and improve cardiorespiratory fitness and weight status among elementary students after school. Methods This quasi-experimental controlled study compared change in moderate-to-vigorous physical activity (MVPA), BMI z-score, and cardiorespiratory fitness (VO2) over 5 months between students in after-school programs exposed to SPARK vs. controls. Participants were 5th grade students at 3 intervention schools (N=48) and 3 control schools (N=52). Results There was no difference between groups in mean change in MVPA, BMI z-score, or cardiorespiratory fitness. After-school time dedicated to physical activity did not increase with the implementation of SPARK. Intervention students’ self-assessment of their activity levels relative to their peers significantly increased compared to control students (p = .011). Conclusions In this 5-month study, the SPARK program did not increase MVPA in the after-school setting. Increasing the amount of time dedicated to physical activity may be as important as the curriculum used to effectively increase physical activity after school.