Sarcosine treatment for oppositional defiant disorder symptoms of attention deficit hyperactivity disorder children
This study aimed to assess the efficacy of sarcosine in treating children with ADHD. We conducted a six-week, randomized, double-blind, placebo-controlled clinical trial. The primary outcome measures were those on the Inattention, Hyperactivity/impulsivity, and oppositional defiant disorder (ODD) subscales of the Swanson, Nolan, and Pelham, version IV scale. Efficacy and safety were measured bi-weekly. A total of 116 children with ADHD were enrolled. Among them, 48 (83%) of the 58 sarcosine recipients and 44 (76%) of the 58 placebo recipients returned for the first post-treatment visit. The missing data values were imputed...
Source: Journal of Psychopharmacology - September 22, 2016 Category: Psychiatry Authors: Tzang, R.-F., Chang, Y.-C., Tsai, G. E., Lane, H.-Y. Tags: Original Papers Source Type: research
Pharmacotherapy of conduct disorder: Challenges, options and future directions
There is a critical need for evaluation of the pharmacotherapies used in conduct disorder (CD), due to the high incidence of off-label prescribing. The aim of this review was to identify concerns associated with the safety, efficacy and impact on quality of life (QOL) that pharmacotherapy has in children and adolescents with CD. A systematic review was undertaken using pre-defined search criteria and four databases, including reference searches. We assessed these studies using the Strength of Recommendation Taxonomy, Grading of Recommendations Assessment, Development and Evaluation, and Review Manager Risk of Bias (RevMan&...
Source: Journal of Psychopharmacology - September 22, 2016 Category: Psychiatry Authors: Hambly, J. L., Khan, S., McDermott, B., Bor, W., Haywood, A. Tags: Reviews Source Type: research
A neurological perspective on the enhancement debate: Lessons learned from Parkinsons disease
Cognitive enhancement is signified by adaptive behavioural change following an intervention that targets the brain. Although much of the discussion and research into cognitive enhancement focuses on the effects of neural interventions in healthy individuals, it is useful to consider evidence from clinical populations. Diseases of the central nervous system represent the primary and richest source of evidence on the effects of brain manipulations, which are in the first instance therapeutic. Parkinson’s disease (PD) is used as a model for understanding the effects of pharmacological agents that target systems with a c...
Source: Journal of Psychopharmacology - September 22, 2016 Category: Psychiatry Authors: Kehagia, A. A. Tags: Reviews Source Type: research
Involvement of medial prefrontal cortex alpha-2 adrenoceptors on memory acquisition deficit induced by arachidonylcyclopropylamide, a cannabinoid CB1 receptor agonist, in rats; possible involvement of Ca2+ channels
In conclusion, these data indicate that mPFC alpha-2 adrenoceptors play an important role in ACPA-induced amnesia and Ca2+ channels have a critical role this phenomenon. (Source: Journal of Psychopharmacology)
Source: Journal of Psychopharmacology - August 21, 2016 Category: Psychiatry Authors: Beiranvand, A., Nasehi, M., Zarrindast, M.-R., Moghaddasi, M. Tags: Original Papers Source Type: research
Modulation of cannabinoid signaling by hippocampal 5-HT4 serotonergic system in fear conditioning
Behavioral studies have suggested a key role for the cannabinoid system in the modulation of conditioned fear memory. Likewise, much of the literature has revealed that the serotonergic system affects Pavlovian fear conditioning and extinction. A high level of functional overlap between the serotonin and cannabinoid systems has also been reported. To clarify the interaction between the hippocampal serotonin (5-HT4) receptor and the cannabinoid CB1 receptor in the acquisition of fear memory, the effects of 5-HT4 agents, arachidonylcyclopropylamide (ACPA; CB1 receptor agonist), and the combined use of these drugs on fear lea...
Source: Journal of Psychopharmacology - August 21, 2016 Category: Psychiatry Authors: Nasehi, M., Farrahizadeh, M., Ebrahimi-Ghiri, M., Zarrindast, M.-R. Tags: Original Papers Source Type: research
Anxiolytic activity of the neuroprotective peptide HLDF-6 and its effects on brain neurotransmitter systems in BALB/c and C57BL/6 mice
This study is focused on a new amide derivative of the peptide HLDF-6 (Thr-Gly-Glu-Asn-His-Arg). This hexapeptide is a fragment of Human Leukaemia Differentiation Factor (HLDF). It displays a broad range of nootropic and neuroprotective activities. We showed, for the first time, that the peptide HLDF-6-amide has high anxiolytic activity. We used ‘open field’ and ‘elevated plus maze’ tests to demonstrate anxiolytic effects of HLDF-6-amide (0.1 and 0.3 mg/kg intranasally), which were comparable to those of the reference drug diazepam (0.5 mg/kg). Five daily equipotent doses of HLDF-6-amide selectively...
Source: Journal of Psychopharmacology - August 21, 2016 Category: Psychiatry Authors: Zolotarev, Y. A., Kovalev, G. I., Kost, N. V., Voevodina, M. E., Sokolov, O. Y., Dadayan, A. K., Kondrakhin, E. A., Vasileva, E. V., Bogachuk, A. P., Azev, V. N., Lipkin, V. M., Myasoedov, N. F. Tags: Original Papers Source Type: research
Anxiolytic effects of GLYX-13 in animal models of posttraumatic stress disorder-like behavior
In the present study, we investigated the effectiveness of GLYX-13, an NMDA receptor glycine site functional partial agonist, to alleviate the enhanced anxiety and fear response in both a mouse and rat model of stress-induced behavioral changes that might be relevant to posttraumatic stress disorder (PTSD). Studies over the last decades have suggested that the hyperactivity of hypothalamic–pituitary–adrenal (HPA) axis is one of the most consistent findings in stress-related disease. Herein, we used these animal models to further investigate the effect of GLYX-13 on the stress hormone levels and glucocorticoid r...
Source: Journal of Psychopharmacology - August 21, 2016 Category: Psychiatry Authors: Jin, Z.-l., Liu, J.-x., Liu, X., Zhang, L.-m., Ran, Y.-h., Zheng, Y.-y., Tang, Y., Li, Y.-F., Xiong, J. Tags: Original Papers Source Type: research
Comparative analysis of pharmacological properties of xanomeline and N-desmethylclozapine in rat brain membranes
Conclusions:
The agonistic effects on the mAChRs (particularly M1 subtype, and also probably M4 subtype), the 5-HT1A receptor and the -opioid receptor expressed in native brain tissues, some of which are common to both compounds and others specific to either, likely shape the unique beneficial effectiveness of both compounds in the treatment for schizophrenic patients. These characteristics provide us with a clue to develop newer antipsychotics, beyond the framework of dopamine D2 receptor antagonism, that are effective not only on positive symptoms but also on negative symptoms and/or cognitive/affective impairment. (Sour...
Source: Journal of Psychopharmacology - August 21, 2016 Category: Psychiatry Authors: Odagaki, Y., Kinoshita, M., Ota, T. Tags: Original Papers Source Type: research
Oral administration of D-alanine in monkeys robustly increases plasma and cerebrospinal fluid levels but experimental D-amino acid oxidase inhibitors had minimal effect
We report that while oral D-alanine administration to baboons (10 mg/kg) enhanced D-alanine plasma and CSF levels over 20-fold versus endogenous levels, addition of experimental DAAOi to the regimen exhibited a 2.2-fold enhancement in plasma and no measurable effect on CSF levels. The results provide caution regarding the utility of DAAO inhibition to increase D-amino acid levels as treatment for patients with schizophrenia. (Source: Journal of Psychopharmacology)
Source: Journal of Psychopharmacology - August 21, 2016 Category: Psychiatry Authors: Rojas, C., Alt, J., Ator, N. A., Wilmoth, H., Rais, R., Hin, N., DeVivo, M., Popiolek, M., Tsukamoto, T., Slusher, B. S. Tags: Original Papers Source Type: research
Inhibitory effects of imidazoline receptor ligands on basal and kainic acid-induced neurotoxic signalling in mice
This in vivo study assessed the potential of the imidazoline receptor (IR) ligands moxonidine (selective I1-IR), BU224 (selective I2-IR) and LSL61122 (mixed I1/I2-IR) to dampen excitotoxic signalling induced by kainic acid (KA; 45 mg/kg) in the mouse brain (hippocampus and cerebral cortex). KA triggered a strong behavioural syndrome (seizures; maximal at 60–90 minutes) and sustained stimulation (at 72 hours with otherwise normal mouse behaviour) of pro-apoptotic c-Jun-N-terminal kinases (JNK) and calpain with increased cleavage of p35 into neurotoxic p25 (cyclin-dependent kinase 5 [Cdk5] activators) in mouse hippocam...
Source: Journal of Psychopharmacology - August 21, 2016 Category: Psychiatry Authors: Keller, B., Garcia-Sevilla, J. A. Tags: Original Papers Source Type: research
Excessive nest building is a unique behavioural phenotype in the deer mouse model of obsessive-compulsive disorder
Obsessive–compulsive disorder (OCD) is a phenotypically heterogeneous condition characterised by time-consuming intrusive thoughts and/or compulsions. Irrespective of the symptom type diagnosed, the severity of OCD is characterised by heterogeneity in symptom presentation that complicates diagnosis and treatment. Heterogeneity of symptoms would be invaluable in an animal model. Nest building behaviour forms part of the normal behavioural repertoire of rodents and demonstrates profound between-species differences. However, it has been proposed that within-species differences in nest building behaviour (i.e. aberrant v...
Source: Journal of Psychopharmacology - August 21, 2016 Category: Psychiatry Authors: Wolmarans, D. W., Stein, D. J., Harvey, B. H. Tags: Original Papers Source Type: research
Effects of dopamine agents on a schedule-induced polydipsia procedure in the spontaneously hypertensive rat and in Wistar control rats
The spontaneously hypertensive rat (SHR) has been proposed as an animal model for attention deficit hyperactivity disorder (ADHD), and typically develops excessive patterns of response under most behavioural protocols. Schedule-induced polydipsia (SIP) is the excessive water consumption that occurs as a schedule effect when food is intermittently delivered and animals are partially food- but not water-deprived. SIP has been used as a model of excessive behaviour, and considerable evidence has involved the dopaminergic system in its development and maintenance. The aim of this study was to evaluate the effects of the most c...
Source: Journal of Psychopharmacology - August 21, 2016 Category: Psychiatry Authors: Ibias, J., Miguens, M., Pellon, R. Tags: Original Papers Source Type: research
The NK1R-/- mouse phenotype suggests that small body size, with a sex- and diet-dependent excess in body mass and fat, are physical biomarkers for a human endophenotype with vulnerability to attention deficit hyperactivity disorder
The abnormal behaviour of NK1R-/- mice (locomotor hyperactivity, inattentiveness and impulsivity in the 5-Choice Serial Reaction-Time Test) is arguably analogous to that of patients with attention deficit hyperactivity disorder (ADHD). Evidence suggests that small body size and increased body weight are risk factors for ADHD. Here, we compared the body size, body mass and body composition of male and female NK1R-/- mice and their wildtypes that had been fed either standard laboratory chow or a high-fat (45%: ‘Western’) diet. Male NK1R-/- mice from both cohorts were approximately 7% shorter than wildtypes. A sim...
Source: Journal of Psychopharmacology - August 21, 2016 Category: Psychiatry Authors: Pillidge, K., Heal, D. J., Stanford, S. C. Tags: Original Papers Source Type: research
Perseveration by NK1R-/- ('knockout) mice is blunted by doses of methylphenidate that affect neither other aspects of their cognitive performance nor the behaviour of wild-type mice in the 5-Choice Continuous Performance Test
The underlying cause(s) of abnormalities expressed by patients with attention deficit hyperactivity disorder (ADHD) have yet to be delineated. One factor that has been associated with increased vulnerability to ADHD is polymorphism(s) of TACR1, which is the human equivalent of the rodent NK1 (substance P-preferring) receptor gene (Nk1r). We have reported previously that genetically altered mice, lacking functional NK1R (NK1R–/–), express locomotor hyperactivity, which was blunted by the first-line treatment for ADHD, methylphenidate. Here, we compared the effects of this psychostimulant (3, 10 and 30 mg/kg, int...
Source: Journal of Psychopharmacology - August 21, 2016 Category: Psychiatry Authors: Pillidge, K., Porter, A. J., Young, J. W., Stanford, S. C. Tags: Original Papers Source Type: research
Antipsychotics decrease response confidence
Antipsychotics represent the first-choice treatment for schizophrenia. However, the cognitive and emotional pathways through which symptom reduction is achieved have remained unclear. We recently proposed that the induction of doubt is a core mechanism of action of antipsychotics. In the framework of a randomized, double-blind, placebo-controlled, crossover design, 39 nonclinical participants filled out a questionnaire tapping into cognitive and emotional changes (Effect of Antipsychotic Medication on Emotion and Cognition-revised (EAMEC-r)) each time they had received one of three substances (haloperidol, placebo, L-dopa)...
Source: Journal of Psychopharmacology - July 12, 2016 Category: Psychiatry Authors: Moritz, S., Kolbeck, K., Andreou, C. Tags: Short Report Source Type: research
