***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The US National Institute of Neurological Disorders and Stroke convened major stakeholders in June 2012 to discuss how to improve the method ological reporting of animal studies in grant applications and publications . The main workshop recommendation is that at a minimum studies should report on sample -size estimation , whether and how animals were r and omized , whether investigators were blind to the treatment , and the h and ling of data . We recognize that achieving a meaningful improvement in the quality of reporting will require a concerted effort by investigators , review ers , funding agencies and journal editors . Requiring better reporting of animal studies will raise awareness of the importance of rigorous study design to accelerate scientific progress The localization of substance P in brain regions that coordinate stress responses and receive convergent monoaminergic innervation suggested that substance P antagonists might have psychotherapeutic properties . Like clinical ly used antidepressant and anxiolytic drugs , substance P antagonists suppressed  isolation-induced vocalizations in guinea pigs . In a placebo-controlled trial in patients with moderate to severe major depression , robust antidepressant effects of the substance P antagonist MK-869 were consistently observed . In pre clinical studies , substance P antagonists did not interact with monoamine systems in the manner seen with established antidepressant drugs . These findings suggest that substance P may play an important role in psychiatric disorders The pharmacological properties of two NK1 antagonists were studied in comparison with a benzodiazepine during a 7 % CO2 challenge in a population of healthy volunteers selected for a high sensitivity to the challenge . In total , 19 healthy subjects , pre-screened for their responsiveness to the 7 % CO2 test , took part in the r and omised , double-blind , cross-over , incomplete block design study . After receiving treatment or placebo , the volunteers were subjected to three 7 % CO2 challenges each for a time of 20 min . The treatment consisted of the administration of the following three active drugs : a single dose of benzodiazepine alprazolam ( 0.75 mg ) and a single dose of the NK1 antagonists vestipitant ( GW597599 ) ( 15 mg ) and vofopitant ( GR205171 ) ( 25 mg ) . Anxiety during the challenge was evaluated with Visual Analogue Scale-Anxiety ( VAS-A ) and with Panic Symptom List ( PSL III-R ) . Respiratory parameters , heart rate and skin conductance were also recorded . Compared with placebo , vestipitant showed a significant reduction ( p<0.05 ) in anxiety assessed on the VAS-A scale ( ΔVAS-A% ) while alprazolam significantly ( p<0.01 ) attenuated the PSL III-R total score  . Vofopitant did not show any anxiolytic effect . In the comparison analysis between placebo and drugs , none of the respiratory and other physiological parameters showed a statistically significant difference The effects of flesinoxan , a potent and selective 5-HT1A agonist , were studied in two pilot studies in panic disorder patients to explore the role of 5-HT1A receptors in the mechanism of action of antipanic agents . This paper reports on the results of these two studies with flesinoxan . In study I , using a single-blind crossover design , five patients were treated for 1 week with placebo , 4 weeks with flesinoxan ( up to 2.4 mg per day ) , and 2 weeks with placebo .  In study II , 15 patients were enrolled in a double-blind , three-armed study with placebo and two dosages of flesinoxan .  After a single-blind placebo run-in phase of 1 week , patients were treated for 8 weeks with placebo , 0.6 or 1.2 mg/day flesinoxan . In pilot study I patients ’ condition worsened during the 4-week flesinoxan treatment period . Anxiety was frequently reported as an adverse event . Symptoms returned to the pre-treatment level during the 2-week placebo washout period . In pilot study II , no treatment effects in either group were observed . Anxiety as an adverse event was less prominent than in the first pilot study . A lowering of mood was seen in some patients . The sample sizes of these two pilot studies are too small to draw firm conclusions on the efficacy of flesinoxan in panic disorder , but the present data are not encouraging in this respect . The worsening of symptoms seen with the highest dose of flesinoxan is intriguing and might give a clue to the underst and ing of the mechanism underlying similar effects seen with antidepressants in panic disorder patients The neuropeptide substance P and its receptor NK1 have been implicated in emotion , anxiety and stress in pre clinical studies . However , the role of NK1 receptors in human brain function is less clear and there have been inconsistent reports of the value of NK1 receptor antagonists in the treatment of clinical depression . The present study therefore aim ed to investigate effects of NK1 antagonism on the neural processing of emotional information in healthy volunteers . Twenty-four participants were r and omized to receive a single dose of aprepitant ( 125 mg ) or placebo . Approximately 4 h later , neural responses during facial expression processing and an emotional counting Stroop word task were assessed using fMRI .  Mood and subjective experience were also measured using self-report scales . As expected a single dose of aprepitant did not affect mood and subjective state in the healthy volunteers . However , NK1 antagonism increased responses specifically during the presentation of happy facial expressions in both the rostral anterior cingulate and the right amygdala . In the emotional counting Stroop task the aprepitant group had increased activation in both the medial orbitofrontal cortex and the precuneus cortex to positive vs. neutral words . These results suggest consistent effects of NK1 antagonism on neural responses to positive affective information in two different paradigms . Such findings confirm animal studies which support a role for NK1 receptors in emotion . Such an approach may be useful in underst and ing the effects of novel drug treatments prior to full-scale clinical trials Background Systematic Review s ( SRs ) of experimental animal studies are not yet common practice , but awareness of the merits of conducting such SRs is steadily increasing . As animal intervention studies differ from r and omized clinical trials ( RCT ) in many aspects , the methodology for SRs of clinical trials needs to be adapted and optimized for animal intervention studies . The Cochrane Collaboration developed a Risk of Bias ( RoB ) tool to establish consistency and avoid discrepancies in assessing the method ological quality of RCTs . A similar initiative is warranted in the field of animal experimentation . Methods We provide an RoB tool for animal intervention studies ( SYRCLE ’s RoB tool ) . This tool is based on the Cochrane RoB tool and has been adjusted for aspects of bias that play a specific role in animal intervention studies . To enhance transparency and applicability , we formulated signalling questions to facilitate judgment . Results The result ing RoB tool  for animal studies contains 10 entries . These entries are related to selection bias , performance bias , detection bias , attrition bias , reporting bias and other biases . Half these items are in agreement with the items in the Cochrane RoB tool . Most of the variations between the two tools are due to differences in design between RCTs and animal studies . Shortcomings in , or unfamiliarity with , specific aspects of experimental design of animal studies compared to clinical studies also play a role . Conclusions SYRCLE ’s RoB tool is an adapted version of the Cochrane RoB tool . Widespread adoption and implementation of this tool will facilitate and improve critical appraisal of evidence from animal studies . This may subsequently enhance the efficiency of translating animal research into clinical practice and increase awareness of the necessity of improving the method ological quality of animal studies 
    Output:
    
Meta- analysis showed that the different drug classes in clinical use for the treatment of anxiety disorders , have comparable effects on vocalization behaviour , irrespective of their mechanism of action .
Of the experimental drugs , nociception ( NOP ) receptor agonists proved very effective in this test .
With regard to method ological characteristics , repeated testing of pups as well as selecting pups with moderate or high levels of vocalization were associated with larger treatment effects .