Selective serotonin receptor stimulation of the medial nucleus accumbens differentially affects appetitive motivation for food on a progressive ratio schedule of reinforcement

Previously, we reported that stimulation of selective serotonin (5-HT) receptor subtypes in the nucleus accumbens shell differentially affected consumption of freely available food. Specifically, activation of 5-HT₆ receptors caused a dose-dependent increase in food intake, while the stimulation of 5-HT_1/7 receptor subtypes decreased feeding [34]. The current experiments tested whether similar pharmacological activation of nucleus accumbens serotonin receptors would also affect appetitive motivation, as measured by the amount of effort non-deprived rats exerted to earn sugar reinforcement. Rats were trained to lever press for sugar pellets on a progressive ratio 2 schedule of reinforcement. Across multiple treatment days, three separate groups (N = 8–10) received bilateral infusions of the 5-HT₆ agonist EMD 386088 (at 0.0, 1.0 and 4.0 μg/0.5 μl/side), the 5-HT_1/7 agonist 5-CT (at 0, 0.5, 1.0, or 4.0 μg/0.5 μl/side), or the 5-HT_2C agonist RO 60-0175 fumarate (at 0, 2.0, or 5.0 μg/0.5 μl/side) into the anterior medial nucleus accumbens prior to a 1-h progressive ratio session. Stimulation of 5-HT₆ receptors caused a dose-dependent increase in motivation as assessed by break point, reinforcers earned, and total active lever presses. Stimulation of 5-HT_1/7 receptors increased lever pressing at the 0.5 μg dose of 5-CT, but inhibited lever presses and break point at 4.0 μg/side. Injection of the 5-HT_2C agonist had no effect on motivation within the task. Collectively, these experiments suggest that, in addition to their role in modulating food consumption, nucleus accumbens 5-HT₆ and 5-HT_1/7 receptors also differentially regulate the appetitive components of food-directed motivation.     

Ingested soluble CD14 contributes to the functional pool of circulating sCD14 in mice

Soluble CD14 (sCD14) is a pattern recognition receptor and Toll-like co-receptor observed in human milk (5–26 μg/mL) and other bodily fluids such as blood (3 μg/mL). The most well defined role of sCD14 is to recognize lipopolysaccharide of Gram-negative bacteria and signal an immune response through Toll-like receptor 4 (TLR4). Previous research has shown ingested sCD14 to transfer from the gastrointestinal tract and into the blood stream in neonatal rats. The contribution of human milk sCD14 to circulating levels in the infant and the functionality of the protein, however, remained unknown. Using CD14^−/− mouse pups fostered to wild type (WT) mothers expressing sCD14 in their milk, we show herein that ingestion of sCD14 resulted in blood sCD14 levels up 0.16 ± 0.09 μg/mL. This represents almost one-third (26.7%) of the circulating sCD14 observed in WT pups fostered to WT mothers (0.60 ± 0.14 μg/mL). We also demonstrate that ingested-sCD14 transferred to the blood remains functional in its ability to recognize lipopolysaccharide as demonstrated by a significant increase in immune response (IL-6 and TNF-α) in CD14^−/− pups fostered to WT mothers in comparison to control animals (P = 0.002 and P = 0.007, respectively). Using human intestinal cells (Caco-2), we also observed a significant decrease in sCD14 transcytosis when TLR4 was knocked down (P < 0.001), suggesting sCD14 transfer involves TLR4. The bioavailability of human milk sCD14 established in this report confirms the importance of human milk proteins for the infant and demonstrates the need to improve infant formulas which are lacking in immune proteins such as sCD14.     

Esophageal pressure as an estimate of average pleural pressure with lung or chest distortion in rats

Pressure–volume curves of the lungs and chest wall require knowledge of an effective ‘average’ pleural pressure (Ppl_av), and are usually estimated using esophageal pressure as Pl_es–V and Pw_es–V curves. Such estimates could be misleading when Ppl becomes spatially non-uniform with lung lavage or shape distortion of the chest. We therefore measured Pl_es–V and Pw_es–V curves in conditions causing spatial non-uniformity of Ppl in rats. Pl_es–V curves of normal lungs were unchanged by chest removal. Lung lavage depressed PL_es–V but not Pw_es–V curves to lower volumes, and chest removal after lavage increased volumes at PL ≥ 15 cmH₂O by relieving distortion of the mechanically heterogeneous lungs. Chest wall distortion by ribcage compression or abdominal distension depressed Pw_es–V curves and Pl_es–V curves of normal lungs only at Pl ≥ 3 cmH₂O. In conclusion, Pes reflects Ppl_av with normal and mechanically heterogeneous lungs. With chest wall distortion and dependent deformation of the normal lung, changes of Pl_es–V curves are qualitatively consistent with greater work of inflation.     

Nitric oxide plays a minimal role in hypoxic pulmonary vasoconstriction in isolated rat lungs

The goal of this study was to elucidate the importance of nitric oxide production during hypoxic pulmonary vasoconstriction (HPV). One group of Sprague Dawley rats received an ip injection of saline (controls), while a second group received an ip injection of Escherichia coli lipopolysacharides (LPS-treated) to render them septic. Three hours later, the animals were anesthetized and prepared for the isolated lung experiment. The lungs were ventilated and perfused with diluted autologous blood (Hct 23%) at constant flow rate while monitoring pulmonary arterial pressure (Pa). Nitric oxide production from the lungs was monitored by measuring its concentration in the mixed exhaled gas (NOe) offline. NOe in the isolated lungs was 2 ppb in controls and 90 ppb in the LPS treated lungs. Hypoxia caused Pa to rise from 10 to 17 mmHg in control lungs, and from 10 to 27 mmHg in the LPS treated lungs. NO production was then manipulated to determine if it affects HPV. NOe was increased by adding l-arginine to the blood, and was blocked by adding nitro-l-arginine (LNA). l-Arginine had minimal effect on NOe in control lungs, but increased NOe in LPS treated lungs, and yet HPV was similar in the 2 groups. Despite inhibition of NO synthesis with nitro-l-arginine (LNA), HPV was potentiated equally in control and in LPS treated lungs (Pa rose by 23 mmHg). Thus NO production did not affect the difference in HPV between control and LPS treated lungs. The results suggest that NO does not plays a primary role in HPV.     

Effects of incremental exercise on cerebral oxygenation measured by near-infrared spectroscopy: A systematic review

We conducted a systematic review and meta-regression analysis to quantify effects of exercise on brain hemodynamics measured by near-infrared spectroscopy (NIRS). The results indicate that acute incremental exercise (categorized relative to aerobic capacity (VO₂peak) as low – <30% VO₂peak; moderate – ≥30% VO₂peak to <60% VO₂peak; hard – ≥60% VO₂peak to <VO₂peak; and very hard – ≥VO₂peak intensities) performed by 291 healthy people in 21 studies is accompanied by moderate-to-large increases (mean effect, dz ± 95% CI) in the prefrontal cortex of oxygenated hemoglobin (O₂Hb) or other measures of oxygen level (O₂Hbdiff) or saturation (SCO₂) (0.92 ± 0.67, 1.17), deoxygenated hemoglobin (dHb) (0.87 ± 0.56, 1.19), and blood volume estimated by total hemoglobin (tHb) (1.21 ± 0.84, 1.59). After peaking at hard intensities, cerebral oxygen levels dropped during very hard intensities. People who were aerobically trained attained higher levels of cortical oxygen, dHb, and tHb than untrained people during very hard intensities. Among untrained people, a marked drop in oxygen levels and a small increase in dHb at very hard intensities accompanied declines in tHb, implying reduced blood flow. In 6 studies of 222 patients with heart or lung conditions, oxygenation and dHb were lowered or unchanged during exercise compared to baseline. In conclusion, prefrontal oxygenation measured with NIRS in healthy people showed a quadratic response to incremental exercise, rising between moderate and hard intensities, then falling at very hard intensities. Training status influenced the responses. While methodological improvements in measures of brain oxygen are forthcoming, these results extend the evidence relevant to existing models of central limitations to maximal exercise.     

Reference ranges of lymphocyte subsets in healthy adults and adolescents with special mention of T cell maturation subsets in adults of South Florida

Background

Analysis of peripheral blood lymphocyte subsets has become an essential tool in the evaluation of outcome of diagnostic and research related questions in immunological and pathological conditions. Periodic evaluation and establishment of normal lymphocyte reference ranges are required in clinical and research settings of various immunodeficiency disorders for evaluation of the significance of observations. It is also important that age and gender specific lymphocyte subset reference ranges should be locally established for meaningful comparison and accurate result interpretation as age plays a significant role in the development of immune system.

Methods

We performed dual platform flow cytometry to determine reference ranges for lymphocyte subsets (CD3, CD4, CD8, CD19 [B cells] and CD16+CD56+ [Natural Killer – NK cells]) in 50 adolescents (age range: 12–18) and 100 adults (age range: 21–67) along with T cell maturation, activation and co-stimulatory molecules in healthy multiracial adult population of South Florida.

Results

The lymphocyte reference ranges percentages [absolute counts – Abs, cells/μl] unadjusted for gender differences for adolescents are: CD3: 49–83 [939–2959]; CD4: 27–53 [467–1563]; CD8: 16–40 [259–1262]; CD19+ B cells: 8–31 [169–1297] and CD16+CD56+ NK cells: 3–30 [59–1178] and for adults are: CD3: 65–88 [983–3572]; CD4: 26–62 [491–2000]; CD8: 14–44 [314–2,087]; CD19+ B cells: 2–27 [64–800] and CD16+CD56+ NK cells: 2–27 [27–693]. The ranges for CD4:CD8 ratio for adolescents and adults are 0.7–2.6 and 0.6–4.4, respectively. Gender based analysis of relative percentages of lymphocyte subsets showed no significant differences between adult and adolescent males and females. The mean CD4:CD8 ratio was significantly higher in adult females than males (P = 0.04) and in adolescents this difference was not significant between genders. The mean CD3 and CD4 T cell percentages were higher and CD19 cell percentages were lower in adults compared to adolescents (P < 0.0001). Absolute lymphocyte counts showed a positive correlation with the absolute counts of CD3+, CD4+, CD8+, CD19+, CD16+CD56+, CD45RO+ and CD45RA+ cells (all correlations with P < 0.0001 except CD45RO [P = 0.01] and CD45RA [P = 0.03]).

Conclusion

The reference values of peripheral blood lymphocyte subsets were analyzed in healthy adolescent and adult population of South Florida. This study indicates the need for periodic evaluation and establishment of lymphocyte reference ranges for patient population served based on gender and age since these could influence immune status and treatment outcome.     

Influence of lower body negative pressure release on soleus H reflex,respiratory sensations and reflexes in human subjects

Using a physiological model of acutely increasing venous return into the lungs, i.e. by applying and then releasing lower body negative pressure (LBNP) to mimic the natural stimulus of juxtapulmonary capillary (J) or pulmonary C fibre receptors, produced an immediate and significant reduction in the amplitude of the Hoffman (H) reflex by 81 ± 4% (P = 0.001) in a majority of subjects 70% (n = 5). Accompanying this was a notable change in the respiratory pattern with tidal volume (V_T) increasing in all subjects from (mean) 0.462 ± .038 to 0.777 ± .061 l/min (P = 0.001) and the respiratory rate (F_R) in 40% from 14 ± 1 to 24 ± 0.8 breaths/min. A feeling of pressure in throat, upper chest was reported by all and a shortness of breath-by 70% of the subjects. These were similar in nature to the respiratory sensations felt with threshold doses of intravenous lobeline, a well-established chemical stimulant of J receptors. All effects lasted for 15–20 s and within a minute the parameters resumed their earlier control values.     

Microinjection of different doses of norepinephrine into the caudate putamen produces opposing effects in rats

It has been proven that norepinephrine (NE) regulates antinociception through its action on alpha-adrenoceptors located in brain nuclei, spinal cord, and peripheral organs. However, the supraspinal mechanism of noradrenergic pain modulation is controversial. The present study was aimed at investigating the nociceptive effects induced by injecting different doses of NE and phentolamine into the caudate putamen (CPU) of rats. The thermal pain threshold of the rats was measured by performing a tail-flick test. The tail-flick latency (TFL) was measured at 2–60 min after microinjection of the drugs. Our results revealed that the thermal pain threshold increased (long TFL) after the administration of a low dose of NE (2 μg/2 μl) and decreased (short TFL) after injection of a high dose of NE (8 μg/2 μl). In contrast, the pain threshold decreased after the administration of a low dose of phentolamine (1 μg/2 μl), while it increased after injection of a high dose of phentolamine (4 μg/2 μl). These results indicated that the injection of different doses of NE in the CPU of the rats produced opposite effects on the pain threshold, as determined by the tail-flick tests.     

Short-time lower leg ischemia reduces plantar foot sensitivity

The aim of this study was to investigate the effects of short-time blood flow occlusion on plantar foot vibration sensitivity of healthy young adults. 39 subjects (20 female; 19 male) participated in the study. Blood flow reduction was evoked with a pneumatic tourniquet, placed about 10 cm above the popliteus cavity. Vibration thresholds (200 Hz) were measured at three anatomical locations of the plantar foot (heel, first metatarsal head and hallux) in three different cuff pressure conditions: baseline (0 mmHg), low (50 mmHg) and high (150 mmHg). Each pressure condition was held for 4 min prior to vibration threshold measurements. No reperfusion time was allowed between conditions. The results show a significant increase in vibration thresholds measured at all anatomical locations in the high pressure condition (150 mmHg), whereas low pressure (50 mmHg) caused a significant threshold increase only at the hallux, compared to baseline (0 mmHg) measurements. Short-time blood flow occlusion seems to affect the afferent transmission of vibration stimuli from Vater–Pacini corpuscles, resulting in decreased plantar foot sensitivity. The present study provides an insight into initial adaptations caused by reduced blood flow in plantar foot sensitivity of healthy young adults.     

Activation of the dorsal vagal nucleus increases pancreatic exocrine secretion in the rat

Pancreatic secretion is regulated by the dorsal vagal nucleus (DVN) which is modulated by several neurotransmitters and diverse synaptic inputs. The inhibitory neurotransmitter GABA is a major modulator of the vagal output to the gastrointestinal tract. The present study investigated the effects of GABA_A receptor blockade in the DVN, using bicuculline methiodide (BIM, GABA_A receptor antagonist, 100 pmol/25 nl), on pancreatic exocrine secretion (PES). Male Sprague–Dawley rats anaesthetised with isoflurane were used in all experiments. PES was collected from the common bile-pancreatic duct and was used to determine the pancreatic protein output (PPO). PES and PPO were measured prior to, and after, microinjection of BIM into the DVN. Bilateral microinjection of BIM into the DVN significantly increased PES and PPO from 23.4 ± 3.2 μl/h to 66.1 ± 17.5 μl/h and 19.3 ± 1.7 μg/h to 35.7 ± 3.0 μg/h (P < 0.05), respectively. Atropine methonitrate (100 μg/(kg min), i.v.) blocked the excitatory effect of BIM microinjection on PES and PPO. These results suggest that activation of DVN neurons stimulates pancreatic secretion via a cholinergic muscarinic mechanism.     

Vaccine-induced inflammation attenuates the vascular responses to mental stress

Inflammation is associated with poorer vascular function, with evidence to suggest that inflammation can also impair the vascular responses to mental stress. This study examined the effects of vaccine-induced inflammation on vascular responses to mental stress in healthy participants. Eighteen male participants completed two stress sessions: an inflammation condition having received a typhoid vaccination and a control (non-inflamed) condition. Tumor necrosis factor-alpha and interleukin-6 (p's < .001) increased following vaccination, confirming modest increases in inflammation. Mental stress increased blood flow, blood pressure, heart rate, and cardiac output in both conditions (all p's < .001), but the blood flow response to stress was attenuated having received the vaccination compared to the control condition (p's < .05). These results further implicate the interaction between inflammation and the vasculature as a mechanism through which stress may trigger myocardial infarction.     

Decoding rule from vasoconstrictor skin sympathetic nerve activity to nonglabrous skin blood flow in humans at normothermic rest

Although an importance of vasoconstrictor skin sympathetic nerve activity (SNA) in control of cutaneous circulation is widely recognized, the decoding rule that translate dynamic fluctuations of vasoconstrictor skin SNA into skin blood flow is not fully understood. In 10 male subjects who rested in supine position under normothermic condition, we measured skin blood flow index (by laser-Doppler flowmetry) at the dorsum pedis, and vasoconstrictor skin SNA (by microneurography) that was confirmed to innervate the same region as the flow index. We determined the transfer and coherence functions from the neural activity input to the flow and quantified the contribution and predictability from the input to output by system engineering technique. The results showed that in frequency-domain analysis, the transfer function from vasoconstrictor skin SNA to skin blood flow had low-pass filter characteristics with 3.6 ± 0.1 s of pure time delay. The coherence function was approximately 0.5 between 0.01 and 0.1 Hz and less above 0.1 Hz. In time-domain analysis, the predictability from the SNA to the skin blood flow was approximately 50%. These findings indicate that at normothermic rest, the decoding rule from vasoconstrictor skin SNA to skin blood flow of skin is characterized by low-pass filter with 3–4 s of pure time delay, and that the vasoconstrictor skin SNA contributes to a half of fluctuation of skin blood flow in the condition. The incomplete dependence of skin blood flow on vasoconstrictor skin SNA may confirm nonneural mechanisms to control cutaneous circulation even at normothermic rest.     

Hormonal responses to physical and cognitive stress in a school setting

Little is known about the influence of physical and cognitive stress on the concentration of steroid hormones (SHs) in a school setting. Forty high school students from the 9th grade were randomly assigned to two intervention groups: physical and cognitive stress. Saliva collection took place before (pre-test) and after (post-test) 12 min of high intensity exercise in a defined heart rate (HR) interval (70–85% HR _max; n = 19) and cognitive testing (Letter Digit Span and d2-test, n = 21), respectively. Saliva was analyzed for testosterone (T) and cortisol (C). Results indicated a significant increase of T and C due to a physical but not cognitive stressor. Thus, only the physical stressor was capable of activating the hypothalamic–pituitary–adrenal (HPA) and the hypothalamic–pituitary–gonadal (HPG) axis.     

NOC-9, a selective nitric oxide donor,induces flight reactions in the dorsolateral periaqueductal gray of rats by activating soluble guanylate cyclase

Previous studies have showed that SIN-1, a nitric oxide (NO) donor, injected into the dorsolateral column of the periaqueductal gray (dlPAG) induces flight reactions. This drug, however, can also produce peroxynitrite, which may interfere in this effect. In addition, it is also unknown if this effect is mediated by local activation of soluble guanylate cyclase (sGC). The aims of this study, therefore, were (1) to investigate if NOC-9 (6-(2-Hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-hexanamine), a NO donor that does not produce peroxynitrite, would produce flight reactions after intra-dlPAG administration similar to those induced by SIN-1; (2) to verify if these responses could be prevented by local injection of a selective guanylate cyclase inhibitor (ODQ). Male Wistar rats (n = 5–12) with cannulae aimed at the dlPAG received injections of TRIS (pH 10.0, 0.5 μl), NOC-9 (75 and 150 nmol), saline or SIN-1 (200 nmol) and were placed in an open arena for 10 min. In a subsequent experiment animals (n = 7–8) were pretreated with ODQ (1 nmol/0.5 μl) before receiving NOC-9 150 nmol. NOC-9 induced a significant dose-dependent increase in flight reactions in the first minute after injection (% of animals displaying flight: vehicle = 0%, NOC 75 = 67%, NOC 150 = 75%). SIN-1 had a similar effect (100% of animals showing flight) but the effects lasted longer (10 min) than those of NOC-9. The effect of NOC-9 (150 nmol) was prevented by pretreatment with ODQ (% of animals displaying flight: vehicle + NOC 150 = 71%, ODQ + NOC 150 = 37%). The results suggest that NO donors injected into the dlPAG induce defensive responses that are not mediated by secondary peroxynitrite production. Moreover, they also indicate that these defensive responses depend on activation of local sGC. The data strengthen the proposal that NO can modulate defensive reactions in the dlPAG.     

Bone mineral density in healthy Tunisian women

Interpretation of densitometric results requires a comparison with reference bone mineral density (BMD) values of normal age and sex-matched persons. Thus the aim of this study was to determine these values for healthy Tunisian women, to estimate the prevalence of osteoporosis and to compare our findings with other populations. A cross-sectional study of 1378 Tunisian women aged between 20 and 96 years was carried out using DXA (GE-Lunar Prodigy). Subjects with suspected conditions affecting bone metabolism were excluded. Measurements were taken at the lumbar spine and femoral neck. These values were expressed at T-scores, with reference to the mean BMD values of the group aged 20–40 years. The peak bone mass, estimated in this age group was 1.174 + 0.127 g/cm² at the lumbar spine and 1.016 ± 0.118 g/cm² at the femoral site. It was attained respectively within the age of 25 years and 36 years. For both sites, the expected decline in BMD was shown when the successive age groups [40–49 years] and [50–59 years] were compared. Bone loss was rapid during the first 5 years after menopause. Thereafter BMD declined slowly but continually. The prevalence of osteoporosis in the women over 50 years of age, taking account of peak bone mass observed in our cohort, was 23.3% at the spine and 17.3% at the femoral neck with a combined prevalence of 23.4%. These rates attained respectively 30.4%, 11.8% and 32.9% when we considered the Italian values, which demonstrate the variability of osteodensitometric depending to the reference population adopted.     

Brain prostaglandin formation is increased by α-synuclein gene-ablation during global ischemia

We have previously demonstrated that α-synuclein (Snca) gene ablation reduces brain arachidonic acid (20:4n − 6) turnover rate in phospholipids through modulation of endoplasmic reticulum-localized acyl-CoA synthetase activity. Although 20:4n − 6 is a precursor for prostaglandin (PG), Snca effect on PG levels is unknown. In the present study, we examined the effect of Snca ablation on brain PG level at basal conditions and following 30 s of global ischemia. Brain PG were extracted with methanol, purified on C₁₈ cartridges, and analyzed by LC–MS/MS. We demonstrate, for the first time, that Snca gene ablation did not affect brain PG mass under normal physiological conditions. However, total PG mass and masses of individual PG were elevated ∼2-fold upon global ischemia in the absence of Snca. These data are consistent with our previously observed reduction in 20:4n − 6 recycling through endoplasmic reticulum-localized acyl-CoA synthetase in the absence of Snca, which may result in the increased 20:4n − 6 availability for PG production in the absence of Snca during global ischemia and suggest a role for Snca in brain inflammatory response.     

Role of spinal metabotropic glutamate receptors in regulation of lower urinary tract function in the decerebrate unanesthetized rat

The role of spinal metabotropic glutamate receptors (mGluRs) in control of lower urinary tract functions was evaluated in rats using an mGluR antagonist administered via the intrathecal route. Cystometrograms in combination with external urethral sphincter (EUS) EMG recordings were performed on 13 decerebrate unanesthetized Sprague–Dawley female rats (n = 6 for spinal cord intact rats; n = 7 for spinal cord transected rats). In spinal cord intact rats, a group I/II mGluR antagonist, (±)-alpha-methyl-4-carboxyphenylglycine (MCPG), at doses of 3–30 μg, changed neither bladder nor EUS EMG activity, whereas a larger dose (100 μg) produced a significant facilitation of EUS EMG activity (41% increase in the peak activity) with little effect on bladder contractions. In chronically spinal cord transected rats, MCPG (3–100 μg) had no effect on bladder and EUS EMG activity. The results suggest that group I/II mGluRs are likely to be involved in inhibition of the excitatory pathway to the EUS but not involved in the control of the bladder. The lack of effect of MCPG on the EUS EMG activity in chronic spinal cord transected rats indicates that mGluR-mediated inhibitory control of the EUS was eliminated after spinal cord injury.     

Long term depression of MNTB-LSO synapses is expressed postsynaptically in developing circling mice

Early onset long term depression (LTD) during the first postnatal week has rarely been demonstrated at the medial nucleus of trapezoid body (MNTB) – lateral superior olive (LSO) synapses in spite of many favorable conditions, such as depolarizing synapses and glutamate co-release from MNTB terminals. Thus, we tested the early expression of LTD at MNTB-LSO synapses during the first postnatal week using circling mice, whose main transmitter is glutamate at MNTB-LSO synapses. Tetanic stimulation on MNTB elicited LTD of postsynaptic currents recorded at LSO neurons in P0–P3 homozygous (cir/cir) mice (45.8 ± 0.3% of the control, n = 7) and heterozygous (+/cir) mice (43.3 ± 0.4% of the control, n = 7). The magnitude of LTD decreased in P8–P12 heterozygous (+/cir) mice (84.5 ± 0.3% of the control, n = 7), but was maintained in P8–P12 homozygous (cir/cir) mice (38.2 ± 0.3% of the control, n = 9). Glutamatergic LTD observed in homozygous (cir/cir) mice and glycinergic LTD observed heterozygous (+/cir) mice showed similar pattern of change. As currents induced by the pressure application of glycine on LSO neurons were reduced by tetanic stimulation in P0–P3 heterozygous (+/cir) mice, LTD was thought to occur at postsynaptic sites. Our results suggest that LTD might occur in vivo and participate in the synaptic silencing and strengthening of MNTB-LSO synapses, which is most active during the first postnatal week.     

A meta-analysis of nonrandomized effectiveness studies on outpatient cognitive behavioral therapy for adult anxiety disorders

Objective

The primary aim of this study was to assess the overall effectiveness of individual and group outpatient cognitive behavioral therapy (CBT) for adults with a primary anxiety disorder in routine clinical practice.

Method

We conducted a random effects meta-analysis of 71 nonrandomized effectiveness studies on outpatient individual and group CBT for adult anxiety disorders. Standardized mean gain effect sizes pre- to posttreatment, and posttreatment to follow-up are reported for disorder-specific symptoms, depression, and general anxiety. The mean dropout from CBT is reported.

Results

Outpatient CBT was effective in reducing disorder-specific symptoms in completer (d = 0.90–1.91) and intention-to-treat samples (d = 0.67–1.45). Moderate to large (d = 0.54–1.09) and small to large effect sizes (d = 0.42–0.97) were found for depressive and general anxiety symptoms posttreatment. Across all anxiety disorders, the weighted mean dropout rate was 15.06%. Posttreatment gains for disorder-specific anxiety were maintained 12 months after completion of therapy.

Conclusions

CBT for adult anxiety disorders is very effective and widely accepted in routine practice settings. However, the methodological and reporting quality of nonrandomized effectiveness studies must be improved.