Impact of Serine Racemase Deletion on Nicotine Discrimination.

Introduction: The high comorbidity between schizophrenia and cigarette smoking points to a possible shared heritable factor predisposing individuals with schizophrenia to nicotine addiction. The N-methyl-d-aspartate (NMDA) receptor has been highly implicated in both schizophrenia and nicotine addiction.

Methods: In the present study, we used mice with a null mutation on the serine racemase gene (srr), an established risk gene for schizophrenia, which encodes the enzyme to produce the NMDA receptor co-agonist d-serine, to model the pathology of schizophrenia and to determine whether NMDA receptor hypofunction reduced the ability of srr-/- mice to identify nicotine's subjective effects.

A second space age spanning omics, platforms and medicine across orbits.

The recent acceleration of commercial, private and multi-national spaceflight has created an unprecedented level of activity in low Earth orbit, concomitant with the largest-ever number of crewed missions entering space and preparations for exploration-class (lasting longer than one year) missions. Such rapid advancement into space from many new companies, countries and space-related entities has enabled a 'second space age'. This era is also poised to leverage, for the first time, modern tools and methods of molecular biology and precision medicine, thus enabling precision aerospace medicine for the crews.

Reinforcing and adverse observable effects of nicotine and minor tobacco alkaloids in squirrel monkeys.

The most prevalent psychoactive chemical in tobacco smoke is nicotine, which has been shown to maintain tobacco consumption as well as cause acute adverse effects at high doses, like nausea and emesis. Recent studies in laboratory animals have suggested that many non-nicotine constituents of tobacco smoke (e.g.

Effects of cannabinoid agonists and antagonists in male rats discriminating the synthetic cannabinoid AM2201.

The synthetic forms of delta-9-tetrahydrocannabinol (Δ-THC), dronabinol or nabilone, have been approved to treat several indications. However, due to safety concerns their clinical utility remains limited. Consequently, there is a need for developing cannabinoid (CB) ligands that display better behavioral pharmacological profiles than Δ-THC.

Complex 33-beam simulated galactic cosmic radiation exposure impacts cognitive function and prefrontal cortex neurotransmitter networks in male mice.

Astronauts will encounter extended exposure to galactic cosmic radiation (GCR) during deep space exploration, which could impair brain function. Here, we report that in male mice, acute or chronic GCR exposure did not modify reward sensitivity but did adversely affect attentional processes and increased reaction times. Potassium (K+)-stimulation in the prefrontal cortex (PFC) elevated dopamine (DA) but abolished temporal DA responsiveness after acute and chronic GCR exposure.

Circuits and Biomarkers of the Central Nervous System Relating to Astronaut Performance: Summary Report for a NASA-Sponsored Technical Interchange Meeting.

Biomarkers, ranging from molecules to behavior, can be used to identify thresholds beyond which performance of mission tasks may be compromised and could potentially trigger the activation of countermeasures. Identification of homologous brain regions and/or neural circuits related to operational performance may allow for translational studies between species. Three discussion groups were directed to use operationally relevant performance tasks as a driver when identifying biomarkers and brain regions or circuits for selected constructs.

A contemporaneous narrative review of Fournier's gangrene.

Introduction: Fournier's gangrene is a necrotizing infection of the external genitalia, perineal or perianal regions and is mainly seen in males. Its main risk factors include diabetes, chronic alcoholism, HIV and other immune-compromised states. Fournier's gangrene has an aggressive course associated with a mortality rate of 20%-30%, making early diagnosis and management very important.

Effects of the cannabinoid CB-receptor neutral antagonist AM4113 and antagonist/inverse agonist rimonabant on fentanyl discrimination in male rats.

Evidence suggests the existence of a functional interaction between endogenous cannabinoid (CB) and opioid systems. Thus, targeting CB receptors might be a viable approach to develop new medications for opioid use disorders (OUD). The present studies were undertaken to evaluate the effects of the neutral CB antagonist AM4113 and the CB antagonist/inverse agonist rimonabant in male rats trained to discriminate 0.

Impact of spaceflight stressors on behavior and cognition: A molecular, neurochemical, and neurobiological perspective.

The response of the human body to multiple spaceflight stressors is complex, but mounting evidence implicate risks to CNS functionality as significant, able to threaten metrics of mission success and longer-term behavioral and neurocognitive health. Prolonged exposure to microgravity, sleep disruption, social isolation, fluid shifts, and ionizing radiation have been shown to disrupt mechanisms of homeostasis and neurobiological well-being. The overarching goal of this review is to document the existing evidence of how the major spaceflight stressors, including radiation, microgravity, isolation/confinement, and sleep deprivation, alone or in combination alter molecular, neurochemical, neurobiological, and plasma metabolite/lipid signatures that may be linked to operationally-relevant behavioral and cognitive performance.

A systematic review and meta-analysis of risk factors and treatment choices in emphysematous pyelonephritis.

Purpose: Emphysematous pyelonephritis (EPN) is an acute, severe necrotising infection of the kidney. There has been a shift from early nephrectomy to conservative methods. We conducted a meta-analysis to assess the impact of risk factors and treatment choices on outcomes in EPN.

Nonhuman primate models in the study of spaceflight stressors: Past contributions and future directions.

Studies in rodents suggest that exposure to distinct spaceflight stressors (e.g., space radiation, isolation/confinement, microgravity) may have a profound impact on an astronaut's ability to perform both simple and complex tasks related to neurocognitive performance, central nervous system (CNS) and vestibular/sensorimotor function.

Differential Effects of Nicotine and Nicotine Withdrawal on Fear Conditioning in Male Rats.

Background: Tobacco use is prevalent in individuals who are routinely exposed to stress. However, little is known about how nicotine affects responses to trauma. We examined in rats how nicotine exposure affects fear conditioning, a procedure often used to study stress-related psychiatric illness.

Involvement of Nicotinic Receptor Subtypes in the Behavioral Effects of Nicotinic Drugs in Squirrel Monkeys.

Evidence suggests that the 42, but not the 7, subtype of the nicotinic acetylcholine receptor (nAChR) plays a key role in mediating the behavioral effects of nicotine and related drugs. However, the importance of other nAChR subtypes remains unclear. The present studies were conducted to examine the involvement of nAChR subtypes by determining the effects of selected nicotinic agonists and antagonists in squirrel monkeys either 1) responding for food reinforcement or 2) discriminating the nicotinic agonist (+)-epibatidine (0.

Behavioral phenotyping and dopamine dynamics in mice with conditional deletion of the glutamate transporter GLT-1 in neurons: resistance to the acute locomotor effects of amphetamine.

Rationale: GLT-1 is the major glutamate transporter in the brain and is expressed predominantly in astrocytes but is also present in excitatory axon terminals. To understand the functional significance of GLT-1 expressed in neurons, we generated a conditional GLT-1 knockout mouse and inactivated GLT-1 in neurons using Cre-recombinase expressed under the synapsin 1 promoter, (synGLT-1 KO).

Objectives: Abnormalities of glutamate homeostasis have been shown to affect hippocampal-related behaviors including learning and memory as well as responses to drugs of abuse.

N-Methyl-d-aspartate receptor co-agonist availability affects behavioral and neurochemical responses to cocaine: insights into comorbid schizophrenia and substance abuse.

Both schizophrenia (SZ) and substance abuse (SA) exhibit significant heritability. Moreover, N-methyl-d-aspartate receptors (NMDARs) have been implicated in the pathophysiology of both SZ and SA. We hypothesize that the high prevalence of comorbid SA in SZ is due to dysfunction of NMDARs caused by shared risk genes.

Further delineation between typical and atypical dopamine uptake inhibitors: effects on food-maintained behavior and food consumption.

The present studies compared the acute effects of benztropine analogs (4-Cl-BZT, JHW 007, AHN 1-055), which are atypical dopamine uptake inhibitors, with those of the standard dopamine uptake inhibitors GBR 12909 and cocaine, on the reinforcing efficacy of food and food intake in male Sprague-Dawley rats. Repeated drug effects of JHW 007 on food intake were also determined. The number of ratios completed under a progressive-ratio schedule of food delivery was used as an index of reinforcing efficacy.

Nicotinic effects of tobacco smoke constituents in nonhuman primates.

Rationale: Recent studies in rodents suggest that non-nicotine constituents of tobacco smoke (e.g., minor tobacco alkaloids) may promote tobacco consumption-either through their own pharmacological effects or by augmenting the effects of nicotine.

Effects of the Nanoparticle-Based Vaccine, SEL-068, on Nicotine Discrimination in Squirrel Monkeys.

A key feature of addiction to nicotine likely resides in its ability to produce subjective effects that, in turn, may be reflected in its discriminative-stimulus properties. Vaccination against such effects of nicotine offers an intriguing therapeutic approach for smoking cessation, but a reliably effective and immunologically safe vaccine remains to be identified. Here we report on the ability of SEL-068, a nanoparticle-based vaccine that targets nicotine, to modify the discriminative-stimulus effects of nicotine in a primate species.

Impact of Cytomegalovirus on Long-term Mortality and Cancer Risk After Organ Transplantation.

Background: There is conflicting evidence of the effect of cytomegalovirus (CMV) infection on survival and the risk of cancer after transplantation.

Methods: All recipients of kidney, liver, heart, and lung transplants in the United Kingdom between 1987 and 2007 with known CMV immunoglobulin G status were identified from the U.K.

Donor transmitted and de novo cancer after liver transplantation.

Cancers in solid organ recipients may be classified as donor transmitted, donor derived, de novo or recurrent. The risk of donor-transmitted cancer is very low and can be reduced by careful screening of the donor but cannot be abolished and, in the United Kingdom series is less than 0.03%.

Methamphetamine-like discriminative-stimulus effects of nicotinic agonists.

Nicotine was recently shown to engender d-methamphetamine (MA)-like discriminative-stimulus effects in rats, which may be indicative of shared psychomotor stimulant properties. To further investigate such overlapping discriminative-stimulus effects, nicotinic agonists varying in efficacy and selectivity were studied in squirrel monkeys that discriminated a moderate intramuscular dose of MA (0.1 mg/kg) from vehicle.