Neurotransmitter Specific Roles in the Basolateral Amygdala and Their Effect on Ethanol-Seeking and Intake

poster abstractRelapse is a major problem in alcoholism treatment. Environmental cues can act as triggers that can reinstate alcohol use. By understanding specific neurochemical processes in the brain we can develop new treatments which will be focused on relapse prevention. Specifically the basolateral amygdala (BLA) which is involved in motivated responding and cue-induced reinstatement is of key interest. The aim of this study was to dissect drinking behaviors in an animal model (Long Evans rats) into two parts: appetitive (related to cue-induced reinstatement) and consummatory (related to primary reinforcement). Using operant chambers, lever pressing was a measure of an appetitive response and intake measured consummatory response. We looked at involvement of specific neurotransmitters in the BLA via microinjections of a dopamine and a glutamate antagonist. After initial lever press training, the rats received weekly microinjections of the two drugs as well as artificial cerebrospinal fluid in a randomized order to study their effects on ethanol (n = 5-8/group) and sucrose (n = 6-11/group) responding. Preliminary findings suggest both neurotransmitter- and behavior- specific effects. That is, manipulations of the BLA do not affect the intake of either sucrose or ethanol. This is consistent with findings suggesting that this area is not involved in processing primary reinforcement. However, the administration of the glutamate antagonist (but not the dopamine antagonist) in the BLA had a tendency to decrease reinforcer-seeking at the highest dose (p<0.09). This effect was not reinforcer specific, suggesting that the BLA glutamate activity may be involved in reinforcer-seeking rather than specifically in ethanol-seeking. Overall, the findings of this study will provide new insight into neurotransmitter function in the BLA, its relationship to alcohol intake, and will hopefully drive future research into development of new drugs that will reduce alcohol cravings and chance of relapse

The Effects of Long-Term Varenicline Administration on Ethanol and Sucrose Seeking and Self-Administration in Male P Rats

Background Varenicline, a partial agonist at α4β2 and full agonist at α7 nicotinic cholinergic receptors, is FDA-approved for treatment of smoking cessation and has been found to reduce alcohol craving in clinical populations. In rodents, varenicline decreases free-choice ethanol (EtOH) intake with somewhat mixed findings in operant paradigms that utilize a combined appetitive/consummatory response. Methods The present experiment utilized an operant paradigm that procedurally separates appetitive from consummatory responding and a “reward-blocking” approach (i.e., rats were able to consume EtOH during treatment) to better understand the efficacy of varenicline as a treatment for EtOH self-administration and subsequent EtOH seeking. Separate groups of EtOH- and sucrose-reinforced alcohol-preferring, male P rats experienced alternating cycles of vehicle (2-week cycles) and varenicline (0.3, 1.0, and 2.0 mg/kg self-administered in a gelatin preparation) treatment (3-week cycles) prior to daily sessions where a single lever press resulted in 20 minutes of reinforcer access. At the end of each cycle, a single extinction session assessed the seeking response in the absence of drug pretreatment. Results Varenicline dose dependently decreased EtOH intake. Sucrose intake was largely unaffected, with no overall treatment effects and only sporadic days where the medium and high dose differed from vehicle. Neither sucrose nor EtOH seeking was significantly decreased by varenicline, and there were no treatment effects on either lick or lever-press latency. Overall effect sizes were much greater for both drinking and seeking in the EtOH group as compared to the sucrose group. Conclusions Varenicline effectively attenuates EtOH self-administration during treatment, but the experience with EtOH consumption while varenicline is “on board” is not sufficient to alter subsequent EtOH seeking. The overall pattern of findings indicates that varenicline blocks the rewarding properties of EtOH while not substituting for EtOH, that the nonspecific effects on an alternate reinforcer are negligible, and that blood levels of varenicline need to be maintained in order for treatment to remain effective

Differential COMT expression and behavioral effects of COMT inhibition in male and female Wistar and alcohol preferring rats

Polymorphisms of the catechol-O-methyl transferase (COMT) gene have been associated with alcoholism, suggesting that alterations in the metabolism of catecholamines may be a critical component of the neuropathology of alcoholism. In the current experiments, the COMT inhibitor tolcapone was utilized in an operant behavioral model of reinforcer-seeking and drinking to determine if this compound was capable of remediating the excessive seeking and drinking phenotype of the alcohol-preferring P rat. Tolcapone was administered to male and female alcohol-reinforced P and Wistar rats. Additionally, tolcapone was administered to male sucrose-reinforced P and Wistar rats to determine if its effects also extended to a natural reinforcer. Animals were trained to make an operant response that resulted in 20 min uninterrupted access to the reinforcer solutions. Tolcapone had no effect in female rats on either seeking or consumption of ethanol. However, reductions of both reinforcer seeking and consumption were observed in male P rats, but only of seeking in Wistars. In separate experiments, using reinforcer naïve male and female animals, COMT expression was assessed via Western Blot analysis. Sex differences in COMT expression were also observed, where male P rats exhibited a marked reduction in protein expression relative to females in the PFC. Sex differences were not observed for Wistars or in the striatum and hippocampus. These data complement our previous findings in which tolcapone reduced cue-evoked responses in P rats and further suggest clinical utility of COMT inhibitors in the treatment of addiction disorders, specifically in male high drinkers

Lunar Surface Electric Potential Changes Associated with Traversals through the Earth's Foreshock

We report an analysis of one year of Suprathermal Ion Detector Experiment (SIDE) Total Ion Detector (TID) resonance events observed between January 1972 and January 1973. The study includes only those events during which upstream solar wind conditions were readily available. The analysis shows that these events are associated with lunar traversals through the dawn flank of the terrestrial magnetospheric bow shock. We propose that the events result from an increase in lunar surface electric potential effected by secondary electron emission due to primary electrons in the Earth's foreshock region (although primary ions may play a role as well). This work establishes (1) the lunar surface potential changes as the Moon moves through the terrestrial bow shock, (2) the lunar surface achieves potentials in the upstream foreshock region that differ from those in the downstream magnetosheath region, (3) these differences can be explained by the presence of energetic electron beams in the upstream foreshock region and (4) if this explanation is correct, the location of the Moon with respect to the terrestrial bow shock influences lunar surface potential

Electrification of wind-blown sand on Mars and its implications for atmospheric chemistry

Wind-blown sand, or 'saltation,' creates sand dunes, erodes geological features, and could be a significant source of dust aerosols on Mars. Moreover, the electrification of sand and dust in saltation, dust storms, and dust devils could produce electric discharges and affect atmospheric chemistry. We present the first calculations of electric fields in martian saltation, using a numerical model of saltation that includes sand electrification, plasma physics, and the adsorption of ions and electrons onto particulates. Our results indicate that electric discharges do not occur in martian saltation. Moreover, we find that the production of hydrogen peroxide and the dissociation of methane by electric fields are less significant than previously thought. Both these species are highly relevant to studies of past and present life on Mars.Comment: 5 journal pages, 3 figures, published in Geophysical Research Letter

Emission of non‐thermal microwave radiation by a Martian dust storm

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94934/1/grl26053.pd

Hill-Chao numbers allow decomposing gamma multifunctionality into alpha and beta components

Biodiversity-ecosystem functioning (BEF) research has provided strong evidence and mechanistic underpinnings to support positive effects of biodiversity on ecosystem functioning, from single to multiple functions. This research has provided knowledge gained mainly at the local alpha scale (i.e. within ecosystems), but the increasing homogenization of landscapes in the Anthropocene has raised the potential that declining biodiversity at the beta (across ecosystems) and gamma scales is likely to also impact ecosystem functioning. Drawing on biodiversity theory, we propose a new statistical framework based on Hill-Chao numbers. The framework allows decomposition of multifunctionality at gamma scales into alpha and beta components, a critical but hitherto missing tool in BEF research; it also allows weighting of individual ecosystem functions. Through the proposed decomposition, new BEF results for beta and gamma scales are discovered. Our novel approach is applicable across ecosystems and connects local- and landscape-scale BEF assessments from experiments to natural settings

PADME (Phobos And Deimos and Mars Environment): A Proposed NASA Discovery Mission to Investigate the Two Moons of Mars

After 40 years of solar system exploration by spacecraft, the origin of Mars's satellites, remains vexingly unknown. There are three prevailing hypotheses concerning their origin: H1: They are captured small bodies from the outer main belt or beyond; H2: They are reaccreted Mars impact ejecta; H3: They are remnants of Mars' formation. There are many variants of these hypotheses, but as stated, these three capture the key ideas and constraints on their nature. So far, data and modeling have not allowed any one of these hypotheses to be verified or excluded. Each one of these hypotheses has important implications for the evolution of the solar system, the formation and evolution of planets and satellites, and the delivery of water and organics to Early Mars and Early Earth. Determining the origin of Phobos and Deimos is identified by the NASA and the NRC Decadal Survey as the most important science goal at these bodies