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Schizophrenia amphetamine

Lauren Luhrs, Cynthia Manlapaz, Karen Kedzie, Sandhya Rao, Sara Cabrera-Ghayouri, John Donello, Daniel Gil
Noradrenergic signaling, through the α2A and α2C adrenergic receptors modulates the cognitive and behavioral symptoms of disorders such as schizophrenia, attention deficit hyperactivity disorder (ADHD), and addiction. However, it is unknown whether the α2B receptor has any significant role in CNS function. The present study elucidates the potential role of the α2B receptor in CNS function via the discovery and use of the first subtype selective α2B antagonist (AGN-209419), and behavioral analyses of α-receptor KO mice...
October 14, 2016: Neuroscience
Ana Popovic, Martin Bauer, Ulrich Sauerzopf, Lucie Bartova, Nicole Praschak-Rieder, Harald H Sitte, Siegfried Kasper, Matthäus Willeit
Sensitization is defined as a process whereby repeated intermittent exposure to a given stimulus results in an enhanced response at subsequent exposures. Next to robust findings of an increased dopamine synthesis capacity in schizophrenia, empirical data and neuroimaging studies support the notion that the mesolimbic dopamine system of patients with schizophrenia is more reactive compared to healthy controls. These studies led to the conceptualization of schizophrenia as a state of endogenous sensitization, as stronger behavioral response and increased dopamine release after amphetamine administration or exposure to stress have been observed in patients with schizophrenia...
September 9, 2016: International Journal of Neuropsychopharmacology
Francesca Managò, Maddalena Mereu, Surjeet Mastwal, Rosa Mastrogiacomo, Diego Scheggia, Marco Emanuele, Maria A De Luca, Daniel R Weinberger, Kuan Hong Wang, Francesco Papaleo
Human genetic studies have recently suggested that the postsynaptic activity-regulated cytoskeleton-associated protein (Arc) complex is a convergence signal for several genes implicated in schizophrenia. However, the functional significance of Arc in schizophrenia-related neurobehavioral phenotypes and brain circuits is unclear. Here, we find that, consistent with schizophrenia-related phenotypes, disruption of Arc in mice produces deficits in sensorimotor gating, cognitive functions, social behaviors, and amphetamine-induced psychomotor responses...
August 23, 2016: Cell Reports
Alaa El-Sayed El-Sisi, Samia Salem Sokkar, Magda El-Sayed El-Sayad, Ehab Sayed Ramadan, Enass Yossef Osman
The implications of oxidative stress and neuro-inflammation in the pathogenesis of schizophrenia have been elucidated. Despite their effectiveness against positive symptoms of schizophrenia, antipsychotics have limited effectiveness against negative and cognitive symptoms and are associated with remarkable adverse effects. The use of celecoxib or omega-3 in schizophrenia may have beneficial effects. This study aimed to evaluate the possible efficacies of celecoxib, omega-3 or the combination of celecoxib+risperidone and omega-3+ risperidone compared to risperidone on the behavior and brain biochemistry in rats...
August 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Karly M Turner, Thomas H J Burne
RATIONALE: Attentional deficits occur in a range of neuropsychiatric disorders, such as schizophrenia and attention deficit hyperactivity disorder. Psychostimulants are one of the main treatments for attentional deficits, yet there are limited reports of procognitive effects of amphetamine in preclinical studies. Therefore, task development may be needed to improve predictive validity when measuring attention in rodents. OBJECTIVES: This study aimed to use a modified signal detection task (SDT) to determine if and at what doses amphetamine could improve attention in rats...
September 2016: Psychopharmacology
Crystal Meehan, Lauren Harms, Jade D Frost, Rafael Barreto, Juanita Todd, Ulrich Schall, Cynthia Shannon Weickert, Katerina Zavitsanou, Patricia T Michie, Deborah M Hodgson
Maternal exposure to infectious agents during gestation has been identified as a significant risk factor for schizophrenia. Using a mouse model, past work has demonstrated that the gestational timing of the immune-activating event can impact the behavioural phenotype and expression of dopaminergic and glutamatergic neurotransmission markers in the offspring. In order to determine the inter-species generality of this effect to rats, another commonly used model species, the current study investigated the impact of a viral mimetic Poly (I:C) at either an early (gestational day 10) or late (gestational day 19) time-point on schizophrenia-related behaviour and neurotransmitter receptor expression in rat offspring...
July 14, 2016: Brain, Behavior, and Immunity
Jared W Young, Arpi Minassian, Mark A Geyer
The quantification of unconditioned motoric activity is one of the oldest and most commonly utilized tools in behavioral studies. Although typically measured in reference to psychiatric disorders, e.g., amphetamine-induced hyperactivity used as a model of schizophrenia, bipolar disorder (BD), and Tourette's syndrome, the motoric behavior of psychiatric patients had not been quantified similarly to rodents until recently. The rodent behavioral pattern monitor (BPM) was reverse-translated for use in humans, providing the quantification of not only motoric activity but also the locomotor exploratory profile of various psychiatric populations...
2016: Current Topics in Behavioral Neurosciences
Robert T Franke, Emilia Tarland, Heidrun Fink, Heinz H Pertz, Jan Brosda
RATIONALE: Recently, we showed that 2-bromoterguride acted as a dopamine D2 receptor partial agonist, a serotonin 5-HT2A and α2C-adrenergic receptor antagonist, and exhibited antidopaminergic efficacy in amphetamine-induced locomotion (AIL) in rats without inducing catalepsy. OBJECTIVE: To extend our knowledge on the antipsychotic effects of 2-bromoterguride, we used convergent preclinical animal models and tests; i.e., conditioned avoidance response (CAR), predictive of antipsychotic-like effects; Fos protein expression, a molecular marker for (atypical) antipsychotic activity; wet dog shake behavior, a test for the in vivo effects of drugs acting on central 5-HT2A receptors; and investigated metabolic changes as a common side effect of atypical antipsychotic drugs (APDs)...
August 2016: Psychopharmacology
Simone M Vieira, Luana R Michels, Katiane Roversi, Vinícia G Metz, Barbra K S Moraes, Eduarda M Piegas, Rodrigo J Freddo, André Gundel, Teresa Dalla Costa, Marilise E Burger, Letícia M Colomé, Sandra E Haas
This work aimed to develop nanocapsules (NC) coated with polysorbate 80 (P80), cationic chitosan (CS) or polyethylene glycol (PEG) using clozapine (CZP) as the drug model. The zeta potential, pH and encapsulation efficiency were directly affected by the CS coating. Using the bag dialysis method, the in vitro CZP release from CS-coated nanocapsules was similar to the PEG-coated at pH 7.4. Nanocapsules coated with PEG and CS exhibited an increased action duration compared to the P80-coated nanocapsules in pseudo-psychosis induced by d,l-amphetamine in rats...
September 1, 2016: Colloids and Surfaces. B, Biointerfaces
Jrgen G Bramness, Eline B Rognli
PURPOSE OF REVIEW: The study reviews publications on the use of methamphetamine and amphetamine in relation to psychotic symptoms, substance-induced psychosis, and primary psychosis published between July 2014 and December 2015. The databases MEDLINE, Embase, and PsycINFO were searched using the terms 'amphetamine psychosis' and 'methamphetamine psychosis' for the time period 1 July 2014 to 31 December 2015. RECENT FINDINGS: There were 37 studies published on the subject during this time period...
July 2016: Current Opinion in Psychiatry
Dan Madularu, Praveen Kulkarni, Jason R Yee, William M Kenkel, Waqqas M Shams, Craig F Ferris, Wayne G Brake
The ovarian hormone estrogen has been implicated in schizophrenia symptomatology. Low levels of estrogen are associated with an increase in symptom severity, while exogenous estrogen increases the efficacy of antipsychotic medication, pointing at a possible interaction between estrogen and the dopaminergic system. The aim of this study is to further investigate this interaction in an animal model of some aspects of schizophrenia using awake functional magnetic resonance imaging. Animals receiving 17β-estradiol and haloperidol were scanned and BOLD activity was assessed in response to amphetamine...
June 2016: Hormones and Behavior
Justine Renard, Michael Loureiro, Laura G Rosen, Jordan Zunder, Cleusa de Oliveira, Susanne Schmid, Walter J Rushlow, Steven R Laviolette
UNLABELLED: Schizophrenia-related psychosis is associated with disturbances in mesolimbic dopamine (DA) transmission, characterized by hyperdopaminergic activity in the mesolimbic pathway. Currently, the only clinically effective treatment for schizophrenia involves the use of antipsychotic medications that block DA receptor transmission. However, these medications produce serious side effects leading to poor compliance and treatment outcomes. Emerging evidence points to the involvement of a specific phytochemical component of marijuana called cannabidiol (CBD), which possesses promising therapeutic properties for the treatment of schizophrenia-related psychoses...
May 4, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Guillermo Horga, Clifford M Cassidy, Xiaoyan Xu, Holly Moore, Mark Slifstein, Jared X Van Snellenberg, Anissa Abi-Dargham
IMPORTANCE: Despite the well-established role of striatal dopamine in psychosis, current views generally agree that cortical dysfunction is likely necessary for the emergence of psychotic symptoms. The topographic organization of striatal-cortical connections is central to gating and integration of higher-order information, so a disruption of such topography via dysregulated dopamine could lead to cortical dysfunction in schizophrenia. However, this hypothesis remains to be tested using multivariate methods ascertaining the global pattern of striatal connectivity and without the confounding effects of antidopaminergic medication...
August 1, 2016: JAMA Psychiatry
Maria Moscoso-Castro, Irene Gracia-Rubio, Francisco Ciruela, Olga Valverde
Schizophrenia is a chronic severe mental disorder with a presumed neurodevelopmental origin, and no effective treatment. Schizophrenia is a multifactorial disease with genetic, environmental and neurochemical etiology. The main theories on the pathophysiology of this disorder include alterations in dopaminergic and glutamatergic neurotransmission in limbic and cortical areas of the brain. Early hypotheses also suggested that nucleoside adenosine is a putative affected neurotransmitter system, and clinical evidence suggests that adenosine adjuvants improve treatment outcomes, especially in poorly responsive patients...
July 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Yue Pei, Aman Asif-Malik, Juan J Canales
Biogenic amines are a collection of endogenous molecules that play pivotal roles as neurotransmitters and hormones. In addition to the "classical" biogenic amines resulting from decarboxylation of aromatic acids, including dopamine (DA), norepinephrine, epinephrine, serotonin (5-HT), and histamine, other biogenic amines, present at much lower concentrations in the central nervous system (CNS), and hence referred to as "trace" amines (TAs), are now recognized to play significant neurophysiological and behavioral functions...
2016: Frontiers in Neuroscience
Clifford M Cassidy, Jared X Van Snellenberg, Caridad Benavides, Mark Slifstein, Zhishun Wang, Holly Moore, Anissa Abi-Dargham, Guillermo Horga
UNLABELLED: Connectivity between brain networks may adapt flexibly to cognitive demand, a process that could underlie adaptive behaviors and cognitive deficits, such as those observed in neuropsychiatric conditions like schizophrenia. Dopamine signaling is critical for working memory but its influence on internetwork connectivity is relatively unknown. We addressed these questions in healthy humans using functional magnetic resonance imaging (during ann-back working-memory task) and positron emission tomography using the radiotracer [(11)C]FLB457 before and after amphetamine to measure the capacity for dopamine release in extrastriatal brain regions...
April 13, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Anett Schumacher, Brindan Sivanandan, Edgor Cole Tolledo, Jacob Woldegabriel, Rutsuko Ito
Repeated exposure to sub-anesthetic doses of ketamine in rats has been shown to induce cognitive deficits, as well as behavioral changes akin to the negative symptoms of schizophrenia, giving much face validity to the use of ketamine administration as a pharmacological model of schizophrenia. This study sought to further characterize the behavioral effects of two different ketamine pre-treatment regimens, focusing primarily on the effects of repeated ketamine administration on novelty processing, a capacity that is disrupted in schizophrenia...
August 1, 2016: Progress in Neuro-psychopharmacology & Biological Psychiatry
S Giovanoli, H Engler, A Engler, J Richetto, J Feldon, M A Riva, M Schedlowski, U Meyer
Maternal immune activation can increase the vulnerability of the offspring to develop neuroimmune and behavioral abnormalities in response to stress in puberty. In offspring of immune-challenged mothers, stress-induced inflammatory processes precede the adult onset of multiple behavioral dysfunctions. Here, we explored whether an early anti-inflammatory intervention during peripubertal stress exposure might prevent the subsequent emergence of adult behavioral pathology. We used an environmental two-hit model in mice, in which prenatal maternal administration of the viral mimetic poly(I:C) served as the first hit, and exposure to sub-chronic unpredictable stress during peripubertal maturation as the second hit...
2016: Translational Psychiatry
Carlos Roncero, Elena Ros-Cucurull, Lara Grau-López, Christian Fadeuilhe, Miguel Casas
OBJECTIVES: Episodes of psychotic agitation are frequent in patients with dual diagnosis, that is, in patients with concomitant psychiatric and substance use disorders. Rapid intervention is needed to treat the agitation at a mild stage to prevent the escalation to aggressive behavior. Inhaled loxapine has been demonstrated to rapidly improve symptoms of mild-to-moderate agitation in adults with psychiatric disorders (schizophrenia and bipolar disorder), but data on patients with dual diagnosis are scarce...
July 2016: Clinical Neuropharmacology
Mohamed Sherif, Rajiv Radhakrishnan, Deepak Cyril D'Souza, Mohini Ranganathan
Some of the most compelling evidence supporting an association between cannabinoid agonists and psychosis comes from controlled laboratory studies in humans. Randomized, double-blind, placebo-controlled, crossover laboratory studies demonstrate that cannabinoid agonists, including phytocannabinoids and synthetic cannabinoids, produce a wide range of positive, negative, and cognitive symptoms and psychophysiologic deficits in healthy human subjects that resemble the phenomenology of schizophrenia. These effects are time locked to drug administration, are dose related, and are transient and rarely necessitate intervention...
April 1, 2016: Biological Psychiatry
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