Goal-directed actions are sensitive to work-related response costs, and dopamine in nucleus accumbens is thought to modulate the exertion of effort in motivated behavior. Dopamine-rich striatal areas such as nucleus accumbens also contain high numbers of adenosine A 2A receptors, and, for that reason, the behavioral and neurochemical effects of the adenosine A 2A receptor agonist CGS 21680 [2-p-(2-carboxyethyl) phenethylamino-5Ј-N-ethylcarboxamidoadenosine] were investigated. Stimulation of accumbens adenosine A 2A receptors disrupted performance of an instrumental task with high work demands (i.e., an interval lever-pressing schedule with a ratio requirement attached) but had little effect on a task with a lower work requirement. Immunohistochemical studies revealed that accumbens neurons that project to the ventral pallidum showed adenosine A 2A receptors immunoreactivity. Moreover, activation of accumbens A 2A receptors by local injections of CGS 21680 increased extracellular GABA levels in the ventral pallidum. Combined contralateral injections of CGS 21680 into the accumbens and the GABA A agonist muscimol into ventral pallidum (i.e., "disconnection" methods) also impaired response output, indicating that these structures are part of a common neural circuitry regulating the exertion of effort. Thus, accumbens adenosine A 2A receptors appear to regulate behavioral activation and effort-related processes by modulating the activity of the ventral striatopallidal pathway. Research on the effort-related functions of these forebrain systems may lead to a greater understanding of pathological features of motivation, such as psychomotor slowing, anergia, and fatigue in depression.
Three cleaning techniques that remove external contamination of human hair are assessed to investigate the potential use of Sr and Pb isotope composition of hair for human provenancing. These techniques are; (i) a centrifugation technique using diiodomethane where hair and soil particles are separated by density difference; (ii) a leaching technique of the hair surface using 2 M HNO 3 acid and (iii) cleaning the hair with chloroform, methanol and ultra pure water. These techniques are validated and are successfully applied to demonstrate the capability of modern and archaeological human scalp hair and modern human facial hair to record Sr and Pb isotope variations related to geographic location. In this study, Sr isotope ratios analysed in modern human scalp hair from a female vegetarian and non-smoker register marked isotopic change on a monthly timescale when an individual moves to locations with contrasting Sr isotope compositions. Pb isotope ratios do not show significant changes after moving locations, possibly due to comparable Pb isotope ratios in the two environments. In contrast, Pb isotopes ratios analysed in facial hair from a male omnivore and smoker record isotopic changes within a two week period when moving between locations with significant differences in environmental Pb isotope compositions. Further research is needed to determine the exact rate of change in isotopic composition in scalp and facial hair in humans with different diets and life styles that move from geographical locations with isotopic contrasting composition.
The results of the present study suggest that the selective inactivation of acetaldehyde blocked the rewarding, but not aversive, effects of ethanol and support the role of this ethanol metabolite in the affective properties of ethanol.
Rationale-Nucleus accumbens dopamine (DA) participates in the modulation of instrumental behavior, including aspects of behavioral activation and effort-related choice behavior. Rats with impaired accumbens DA transmission reallocate their behavior away from food-reinforced activities that have high response requirements and instead select less-effortful types of food-seeking behavior. Although accumbens DA is considered a critical component of the brain circuitry regulating effortrelated processes, emerging evidence also implicates adenosine A 2A receptors.Objective-The present work was undertaken to test the hypothesis that accumbens A 2A receptor stimulation would produce effects similar to those produced by DA depletion or antagonism.Materials and methods-Three experiments assessed the effects of the adenosine A 2A agonist CGS 21680 on performance of a concurrent choice task (lever pressing for preferred food vs. intake of less preferred chow) that is known to be sensitive to DA antagonists and accumbens DA depletions.Results-Systemic injections of CGS 21680 reduced lever pressing but did not increase feeding. In contrast, bilateral infusions of the adenosine A 2A receptor agonist CGS 21680 (6.0-24.0 ng) into the nucleus accumbens decreased lever pressing for the preferred food but substantially increased consumption of the less preferred chow. Injections of CGS 21680 into a control site dorsal to the accumbens were ineffective.Conclusions-Taken together, these results are consistent with the hypothesis that local stimulation of adenosine A 2A receptors in nucleus accumbens produces behavioral effects similar to those induced by accumbens DA depletions. Accumbens adenosine A 2A receptors appear to be a component of the brain circuitry regulating effort-related choice behavior.
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