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PubMed Journal Database | Pharmacology, biochemistry, and behavior RSS

23:51 EDT 18th March 2019 | BioPortfolio

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Showing PubMed Articles 1–25 of 176 from Pharmacology, biochemistry, and behavior

GABA receptors modulate morphine antinociception: Pharmacological and genetic approaches.

Previous studies in our laboratory showed an interaction between the GABAergic and opioid systems involved in the analgesic effect of baclofen (BAC). Furthermore, it is known that sex differences exist regarding various pharmacological responses of morphine (MOR) and they are related to an increased sensitivity to MOR effects in males. The aims of the present study were to evaluate the possible involvement of the GABA receptors in the antinociceptive responses induced by MOR (1, 3 and 9 mg/kg, s.c.) admin...

Multivariate pattern analysis of the neural correlates of smoking cue attentional bias.

The automatic capture of attention by drug cues, or attentional bias, is associated with craving and predicts future drug use. Despite its clinical significance, the neural bases of attentional bias to drug cues is not well understood. To address this gap, we undertook a neuroimaging investigation of the neural correlates of attentional bias towards smoking cues. Twenty-nine adults, including 14 active smokers and 15 non-smokers, completed a spatial cuing task during fMRI. A multivariate pattern analysis (M...

The α2,3-selective potentiator of GABA receptors, KRM-II-81, reduces nociceptive-associated behaviors induced by formalin and spinal nerve ligation in rats.

Clinical evidence indicates that positive allosteric modulators (PAMs) of GABA receptors have analgesic benefit in addition to efficacy in anxiety disorders. However, the utility of GABA receptor PAMs as analgesics is compromised by the central nervous system side effects of non-selective potentiators. A selective potentiator of GABA receptors associated with α2/3 subunits, KRM-II-81(5-(8-ethynyl-6-(pyridin-2-yl)-4H-benzo[f]imidazo[1,5-a][1,4]diazepin-3-yl)oxazole), has demonstrated anxiolytic, anticonvuls...

Acute effect of vaporized Cannabis on sleep and electrocortical activity.

The use of Cannabis for medical purposes is rapidly expanding and is usually employed as a self-medication for the treatment of insomnia disorder. However, the effect on sleep seems to depend on multiple factors such as composition of the Cannabis, dosage and route of administration. Vaporization is the recommended route for the administration of Cannabis for medical purposes; however, there is no published research about the effects of vaporized Cannabis on sleep, neither in laboratory animals, nor in huma...

Morphine administered post-trial can induce potent conditioned morphine effects.

Morphine has substantial pro-dopamine effects and in rodents, this is expressed in behavior as increased locomotor activation. Here we administered post-trial 3 dose levels of morphine (3.0, 5.0 and 10.0 mg/kg) or vehicle either immediately or after a 15 min delay to different groups of rats following a brief (5 min) exposure to a novel test environment. Three post-trial injections were administered on three successive days. One day after the first post-trial morphine injections, the non-drug activity...

The serotonin-2C agonist Lorcaserin delays intravenous choice and modifies the subjective and cardiovascular effects of cocaine: A randomized, controlled human laboratory study.

Lorcaserin is a modestly selective agonist for 2C serotonin receptors (5-HTR) approved for weight-loss therapy. This class can attenuate cue-induced responding and drug taking in preclinical studies, but effects in humans have not been reported.

Dose dependent behavioral effects of acute alcohol administration in zebrafish fry.

The zebrafish is becoming increasingly utilized in behavioral neuroscience as it appears to strike a good compromise between practical simplicity and system complexity. Particularly in alcohol (ethanol) research, the zebrafish has been employed as a translationally relevant model organism. However, the majority of studies investigating the effects of alcohol on brain function and behavior has used adult zebrafish. In the current study, we utilize 6-8 post-fertilization day old larval zebrafish (fry) to inve...

Examination of the Gateway Hypothesis in a rat model.

The Gateway Hypothesis is based on epidemiological data and states there is a progression of drug use from use of a softer drug (e.g., nicotine) to use of a harder drug (e.g., morphine). It has been suggested that this sequence is causal and is relevant to drug prevention policies and programs. The present experiment used an animal model to investigate whether the Gateway Hypothesis involves a causal progression. Subjects were 16 female and 16 male Sprague-Dawley rats with ages comparable to late adolescenc...

Compulsive methamphetamine taking and abstinence in the presence of adverse consequences: Epigenetic and transcriptional consequences in the rat brain.

Methamphetamine addiction is characterized by compulsive binges of drug intake despite adverse life consequences. A model of methamphetamine self-administration that includes contingent footshocks to constitute adverse consequences has helped to segregate rats that reduce or stop lever pressing for methamphetamine (sensitive) from those that continue to lever press for the drug (resistant) in the presence of negative outcomes. We have observed differential DNA hydroxymethylation and increased expression of ...

Enrichment-induced differences in methamphetamine drug discrimination in male rats.

Rats raised in an enriched environment show a decrease in sensitivity to the subjective effects of the psychostimulant d-amphetamine. The purpose of the present study was to determine if environmental enrichment during development alters the subjective effects of the more commonly abused drug methamphetamine. Male Sprague-Dawley rats were raised in either an enriched (EC) or an isolated condition (IC). EC and IC rats were trained on a two-lever operant procedure to discriminate 1.0 mg/kg (i.p.) methamphet...

Oral sazetidine-A, a selective α4β2* nicotinic receptor desensitizing agent, reduces nicotine self-administration in rats.

Sazetidine-A selectively desensitizes α4β2 nicotinic receptors and also has partial agonist effects. We have shown that subcutaneous acute and repeated injections as well as chronic infusions of sazetidine-A significantly reduce intravenous (IV) nicotine self-administration in rats. To further investigate the promise of sazetidine-A as a smoking cessation aid, it is important to determine sazetidine-A effects with oral administration and the time-effect function for its action on nicotine self-administrat...

Lutein prevents corticosterone-induced depressive-like behavior in mice with the involvement of antioxidant and neuroprotective activities.

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, se...

Evaluation of SYA16263 as a new potential antipsychotic agent without catalepsy.

SYA16263 exhibited moderate radioligand binding affinity at the D receptor and produced inhibition of apomorphine-induced climbing behavior in mice with an ED 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. W...

Discriminative stimulus effects of mecamylamine and nicotine in rhesus monkeys: Central and peripheral mechanisms.

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 ...

Responses to positive and aversive stimuli in estrous female rats housed in a seminatural environment: Effects of yohimbine and chlordiazepoxide.

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, ch...

Exogenous progesterone for cannabis withdrawal in women: Feasibility trial of a novel multimodal methodology.

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.

The light-dark task in zebrafish confuses two distinct factors: Interaction between background shade and illumination level preference.

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...

Neuroinflammation in addiction: A review of neuroimaging studies and potential immunotherapies.

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 ...

Effects of nicotine conditioning history on alcohol and methamphetamine self-administration in rats.

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.

Effects of chronic lithium exposure in a modified rodent ketamine-induced hyperactivity model of mania.

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.e., 5-...

Chronic unpredictable mild stress accelerates lipopolysaccharide- induced microglia activation and damage of dopaminergic neurons in rats.

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 unknow...

BDNF-TrkB signaling in the nucleus accumbens plays a role in the risk for psychosis after cannabis exposure during adolescence.

Although epidemiological data suggest that repeated use of cannabis during adolescence may increase the risk for psychosis, its precise molecular mechanisms remain undetermined. In this study, we examined whether brain-derived neurotrophic factor (BDNF) and its receptor TrkB signaling plays a role in the risk for psychosis after exposure of cannabinoid (CB) receptor agonist during adolescence. Repeated administration of the CB receptor agonist WIN55,212-2 (2 mg/kg/day) during adolescence (P35 - P45) signi...

Effects of caffeine ingestion on the diurnal variation of cognitive and repeated high-intensity performances.

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, 1...

CB positive allosteric modulation attenuates Δ-THC withdrawal and NSAID-induced gastric inflammation.

Recently, multiple compounds have been synthesized that target the allosteric binding site(s) of CB These CB 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 CB orthosteric modulators, including Δ-tetrahydrocannabinol (THC). The primary goal of the present study was to evaluate the potential of ZCZ011 to at...

Neuroimmune signaling in alcohol use disorder.

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 n...


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