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Pharmacology, Biochemistry, and Behavior

Ana Lúcia Bertarello Zeni, Anderson Camargo, Ana Paula Dalmagro
Depression is a neuropsychiatry medical condition with high prevalence, in which the hypothalamic-pituitary-adrenal axis dysfunction has been postulated as the main cause. The glucocorticoids can be harmful to the brain, particularly by induction of oxidative stress and glutamatergic damage, therefore antioxidants or neuroprotective agents could have beneficial effects. Lutein (LUT) is a dietary xanthophyll able to arrive in the brain that has been used for therapy of macular degeneration. In this sense, several studies pointed beneficial effects of LUT in the brain, particularly in the hippocampus and prefrontal cortex, key regions in mood regulation...
February 17, 2019: Pharmacology, Biochemistry, and Behavior
An-Li Wang, Owen Y Chao, Yi-Mei Yang, Svenja V Trossbach, Christian P Müller, Carsten Korth, Joseph P Huston, Maria Angelica de Souza Silva
In humans, mutations in the Disrupted-in-schizophrenia 1 (DISC1) gene have been related to psychiatric disorders, including symptoms of abnormal cognitive and emotional behaviors. In our previous studies, overexpression of the human DISC1 gene in rats resulted in schizophrenia-like phenotypes showing deficits in motor learning, impaired cognitive function and dysfunctions of the dopamine system. Here we asked, whether the DISC1 overexpression affects locomotor activity in the open field (OF), anxiety in the elevated plus-maze (EPM), depression-related behavior in the forced swim test (FST), and attention-like/short-term working-memory in the spontaneous alternation behavior (SAB) in the T-maze in transgenic DISC1 (tgDISC1) rats and littermate controls (WT)...
February 16, 2019: Pharmacology, Biochemistry, and Behavior
Barbara A Bricker, Kwame Peprah, Hye J Kang, S Y Ablordeppey
SYA16263 exhibited moderate radioligand binding affinity at the D2 receptor and produced inhibition of apomorphine-induced climbing behavior in mice with an ED50 value of 3.88 mg/kg IP, predicting potential antipsychotic effects in humans. Analysis of plasma and brains from rats injected IP with SYA16263 over the course of 24 h revealed a log [brain]/[plasma] (log BB) at Cmax observed equal to 1.08, indicating that SYA16263 enters the brain and is predicted to cross the blood brain barrier (BBB) readily...
February 12, 2019: Pharmacology, Biochemistry, and Behavior
Colin S Cunningham, Megan J Moerke, Lance R McMahon
Mecamylamine is a non-competitive nicotinic acetylcholine receptor (nAChR) antagonist that has been prescribed for hypertension and as an off-label smoking cessation aid. Here, we examined pharmacological mechanisms underlying the interoceptive effects (i.e., discriminative stimulus effects) of mecamylamine (5.6 mg/kg s.c.) and compared the effects of nAChR antagonists in this discrimination assay to their capacity to block a nicotine discriminative stimulus (1.78 mg/kg s.c.) in rhesus monkeys. Central (pempidine) and peripherally restricted nAChR antagonists (pentolinium and chlorisondamine) dose-dependently substituted for the mecamylamine discriminative stimulus in the following rank order potency (pentolinium > pempidine > chlorisondamine > mecamylamine)...
February 6, 2019: Pharmacology, Biochemistry, and Behavior
Olivia Le Moëne, Anders Ågmo
The behavioral effects of putative anxiolytic and anxiogenic drugs are usually evaluated in highly standardized tests. Here, we determined the effects of such drugs in rats housed in mixed sex groups in a seminatural environment. Sexually receptive female Wistar rats were treated with either the anxiolytic drug chlordiazepoxide (2 mg/kg), the anxiogenic drug yohimbine (1 mg/kg), or saline (1 ml/kg). Different emotional challenges eliciting purportedly positive affect (lavender odor, Mozart's music, chocolate flavored food) or negative affect (white noise, fox odor) were then introduced into the seminatural environment...
February 5, 2019: Pharmacology, Biochemistry, and Behavior
Brian J Sherman, Margaret A Caruso, Aimee L McRae-Clark
BACKGROUND: Sex differences in cannabis use disorder (CUD) and its treatment have been identified. Women report more severe withdrawal and have shown worse treatment outcomes. Ovarian hormones are implicated in these differences and research suggests that exogenous progesterone may be an effective pharmacotherapy. METHODS: The current randomized, placebo-controlled, feasibility trial tested a novel multimodal methodology for administering exogenous progesterone during acute cannabis withdrawal...
January 31, 2019: Pharmacology, Biochemistry, and Behavior
Amanda Facciol, Mahrukh Iqbal, Aishwarya Eada, Steven Tran, Robert Gerlai
The light-dark preference task has been commonly used in rodents to screen for anxiogenic and anxiolytic drugs. However, recent adaptations of the light-dark preference test for zebrafish have produced inconsistent results. Several studies have reported that zebrafish exhibit a preference for light, while others have found a preference for black. We suggest the inconsistencies may be the result of confusing certain parameters of the test leading to improper interpretation. For example, researchers often use "light" interchangeably with "white" and "dark" with "black" when these are two distinct factors: level of illumination vs...
January 27, 2019: Pharmacology, Biochemistry, and Behavior
Milky Kohno, Jeanne Link, Laura E Dennis, Holly McCready, Marilyn Huckans, William F Hoffman, Jennifer M Loftis
Addiction is a worldwide public health problem and this article reviews scientific advances in identifying the role of neuroinflammation in the genesis, maintenance, and treatment of substance use disorders. With an emphasis on neuroimaging techniques, this review examines human studies of addiction using positron emission tomography to identify binding of translocator protein (TSPO), which is upregulated in reactive glial cells and activated microglia during pathological states. High TSPO levels have been shown in methamphetamine use but exhibits variable patterns in cocaine use...
January 26, 2019: Pharmacology, Biochemistry, and Behavior
Patrick A Randall, Brayden Fortino, Y Wendy Huynh, Brady M Thompson, Christopher E Larsen, Mackenzie P Callen, Scott T Barrett, Jennifer E Murray, Rick A Bevins, Joyce Besheer
BACKGROUND: Smoking constitutes a significant public health risk. Alcohol and methamphetamine use disorders are also highly co-morbid with smoking, further increasing negative health outcomes. An important question in determining the underlying neurobiology of nicotine poly-drug use is understanding whether having a positive history with nicotine effects alters later drug-taking behavior. METHODS: The current experiments sought to elucidate whether having an appetitive nicotine conditioning history would affect later alcohol or methamphetamine self-administration...
January 18, 2019: Pharmacology, Biochemistry, and Behavior
Hua Kong, Li Yang, Can He, Jing-Wei Zhou, Wei-Zu Li, Wen-Ning Wu, Han-Qing Chen, Yan-Yan Yin
Parkinson's disease (PD) is a neurodegenerative disorder, which is characterized by microglia activation and dopaminergic neurons affected by inflammatory processes. Inflammation has been recognized to be necessary for initiation and progress of PD. Emerging evidence indicates that NLRP3 inflammasome complex is involved in the recognition and execution of host inflammatory response. Stress is acknowledged to be a predisposing and precipitating factor in some neurodegenerative diseases. However, it is unknown whether chronic unpredictable mild stress (CUMS) sensitized microglia to pro-inflammatory stimuli...
January 15, 2019: Pharmacology, Biochemistry, and Behavior
Jacob T Krug, Adam K Klein, Erin M Purvis, Kathy Ayala, Matthew S Mayes, Lisette Collins, Matthew P A Fisher, Aaron Ettenberg
Bipolar illness is characterized by periods of "mania" - high energy, irritability, and increased psychomotor activation. While the neurobiological investigation of mania has been limited by the lack of reliable animal models, researchers have recently reported that daily subanesthetic doses of ketamine produce a lithium-reversible increase in rodent locomotor activity. Such studies have typically employed short-term (2 week) exposure to daily intraperitoneal-injected lithium and extremely brief (i...
January 15, 2019: Pharmacology, Biochemistry, and Behavior
Susanne Nikolaus, Hans-Jörg Wittsack, Markus Beu, Christina Antke, Hubertus Hautzel, Frithjof Wickrath, Anja Müller-Lutz, Maria Angelica De Souza Silva, Joseph P Huston, Gerald Antoch, Hans-Wilhelm Müller
PURPOSE: The present study assessed the influence of the NMDA receptor (R) antagonist amantadine (AMA) on cerebral dopamine D2/3 R binding in relation to motor and exploratory activity in the rat. METHODS: D2/3 R binding was determined in anaesthetized animals with small animal SPECT in baseline and after challenge with AMA (10 or 40 mg/kg) using [123 I]IBZM as radioligand. Immediately post-challenge and prior to radioligand administration, motor/exploratory behaviors were assessed for 30 min in an open field...
January 11, 2019: Pharmacology, Biochemistry, and Behavior
Youssef Souissi, Makram Souissi, Hamdi Chtourou
The purpose of this study was to evaluate the effects of caffeine ingestion on the daily variation of cognitive (i.e., reaction time (RT), attention) and repeated high-intensity exercise performances. Fifteen active males (age: 20 ± 1 years, height: 174.3 ± 4.3 cm, body-mass: 70.8 ± 3.5 kg) performed cognitive and physical tasks under two different circumstances [after a placebo or caffeine ingestion (6 mg/kg of body-mass)] at six different time-of-day (07 h00, 09 h00, 11 h00, 13 h00, 15 h00 and 17 h00) in a randomized double-blind balanced crossover design...
January 3, 2019: Pharmacology, Biochemistry, and Behavior
K R Trexler, M L Eckard, S G Kinsey
Recently, multiple compounds have been synthesized that target the allosteric binding site(s) of CB1. These CB1 positive allosteric modulators, may capture the benefits of cannabinoid receptor activation without unwanted psychoactive effects, such as sedation. For example, ZCZ011 blocks neuropathic pain, absent the catalepsy, sedation, and hypothermia caused by CB1 orthosteric modulators, including Δ9 -tetrahydrocannabinol (THC). The primary goal of the present study was to evaluate the potential of ZCZ011 to attenuate somatic signs of cannabinoid withdrawal in mice...
December 28, 2018: Pharmacology, Biochemistry, and Behavior
Emma K Erickson, Emily K Grantham, Anna S Warden, R Adron Harris
Alcohol use disorder (AUD) is a widespread disease with limited treatment options. Targeting the neuroimmune system is a new avenue for developing or repurposing effective pharmacotherapies. Alcohol modulates innate immune signaling in different cell types in the brain by altering gene expression and the molecular pathways that regulate neuroinflammation. Chronic alcohol abuse may cause an imbalance in neuroimmune function, resulting in prolonged perturbations in brain function. Likewise, manipulating the neuroimmune system may change alcohol-related behaviors...
December 24, 2018: Pharmacology, Biochemistry, and Behavior
Richard W Foltin, Suzette M Evans, Margaret Haney, Kenneth Carpenter, Gillinder Bedi
Risky decision-making is characteristic of drug users, but little is known about the effects of circumstances, such as abstinence, on risky choice behavior in human drug users. We hypothesized that cocaine users would make more risky choices for cocaine (defined as taking a chance to receive a large number of cocaine doses as opposed to choosing to receive a fixed amount of cocaine) after 3 or 7 days of cocaine abstinence, compared to 1 day of cocaine abstinence. Six male nontreatment-seeking current cocaine smokers were enrolled in a 21-day inpatient within-subject study...
December 22, 2018: Pharmacology, Biochemistry, and Behavior
Alexander B Pupyshev, Maria A Tikhonova, Anna A Akopyan, Michael V Tenditnik, Nina I Dubrovina, Tatyana A Korolenko
The neuroprotective effect of autophagy activation by rapamycin and trehalose was studied in a mouse model of Parkinson's disease (PD) induced by neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Both rapamycin (10 mg/kg/day, 7 days) and trehalose (2% in drinking water, 7 days) increased the expression of LC3-II (a marker of autophagy activation) in the frontal cortex and striatum of normal C57Bl/6J mice, with signs of an additive effect. Autophagy stimulation in the striatum was confirmed by a lysosomal osmotic test...
December 21, 2018: Pharmacology, Biochemistry, and Behavior
Miguel A Luján, Laura Colomar, Ernesto Tarragón, Laura López-Cruz, Raúl Pastor, Laura Font
Drug-associated contexts and discrete cues can trigger motivational states responsible for drug-seeking behavior and relapse. In preclinical research, drug-free conditioned hyperactivity has been used to investigate the expression of memories associated with psychostimulant drug effects. Addictive drugs can produce long-lasting sensitization to their psychomotor actions, a phenomenon known as behavioral sensitization. The neuroplasticity underlying behavioral sensitization appears to be involved in pathological drug pursuit and abuse...
December 17, 2018: Pharmacology, Biochemistry, and Behavior
Karen K Szumlinski, Michal A Coelho, Kaziya M Lee, Tori Tran, Kimberly R Sern, Alexandria Bernal, Tod E Kippin
We previously reported that commercially-sourced C57BL/6J (B6) male mice with a history of adult-onset binge-drinking exhibit anxiety-like behavior in early withdrawal, while the negative affective state incubates during protracted withdrawal in adolescent-onset binge-drinking males. As the results of such studies are potentially confounded by age-related differences in reactivity to environmental stress, we employed a 2-bottle-choice DID procedure (20 and 40% alcohol; 20 min habituation to the drinking cage) to examine the effects of binge-drinking on negative affect in male and female, adult and adolescent, B6 mice from our university colony...
December 7, 2018: Pharmacology, Biochemistry, and Behavior
Elizabeth Ralevski, Ismene Petrakis, Margaret Altemus
BACKGROUND: Prior studies have shown that resting heart rate variability (HRV) is reduced in those with alcohol use disorders (AUD). However, HRV following an acute stressful stimulus (reactive HRV), and the relationship between resting or reactive HRV and drinking, craving and relapse in AUD have received less attention. METHODS: Studies using HRV in relationship to acute or chronic alcohol consumption were included in this review. Manuscripts that related to alcohol in the context of cardiovascular disease were excluded...
December 6, 2018: Pharmacology, Biochemistry, and Behavior
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