Effort-related functions of nucleus accumbens dopamine and associated forebrain circuits

Background Over the last several years, it has become apparent that there are critical problems with the hypothesis that brain dopamine (DA) systems, particularly in the nucleus accumbens, directly mediate the rewarding or primary motivational characteristics of natural stimuli such as food. Hypotheses related to DA function are undergoing a substantial restructuring, such that the classic emphasis on hedonia and primary reward is giving way to diverse lines of research that focus on aspects of instrumental learning, reward prediction, incentive motivation, and behavioral activation. Objective The present review discusses dopaminergic involvement in behavioral activation and, in particular, emphasizes the effort-related functions of nucleus accumbens DA and associated forebrain circuitry. Results The effects of accumbens DA depletions on food-seeking behavior are critically dependent upon the work requirements of the task. Lever pressing schedules that have minimal work requirements are largely unaffected by accumbens DA depletions, whereas reinforcement schedules that have high work (e.g., ratio) requirements are substantially impaired by accumbens DA depletions. Moreover, interference with accumbens DA transmission exerts a powerful influence over effort-related decision making. Rats with accumbens DA depletions reallocate their instrumental behavior away from food-reinforced tasks that have high response requirements, and instead, these rats select a less-effortful type of food-seeking behavior. Conclusions Along with prefrontal cortex and the amygdala, nucleus accumbens is a component of the brain circuitry regulating effort-related functions. Studies of the brain systems regulating effort-based processes may have implications for understanding drug abuse, as well as energy-related disorders such as psychomotor slowing, fatigue, or anergia in depression

Scientific assessment of the use of sugars as cigarette tobacco ingredients: A review of published and other publicly available studies

Sugars, such as sucrose or invert sugar, have been used as tobacco ingredients in American-blend cigarettes to replenish the sugars lost during curing of the Burley component of the blended tobacco in order to maintain a balanced flavor. Chemical-analytical studies of the mainstream smoke of research cigarettes with various sugar application levels revealed that most of the smoke constituents determined did not show any sugar-related changes in yields (per mg nicotine), while ten constituents were found to either increase (formaldehyde, acrolein, 2-butanone, isoprene, benzene, toluene, benzo[k]fluoranthene) or decrease (4-aminobiphenyl, N-nitrosodimethylamine, N-nitrosonornicotine) in a statistically significant manner with increasing sugar application levels. Such constituent yields were modeled into constituent uptake distributions using simulations of nicotine uptake distributions generated on the basis of published nicotine biomonitoring data, which were multiplied by the constituent/nicotine ratios determined in the current analysis. These simulations revealed extensive overlaps for the constituent uptake distributions with and without sugar application. Moreover, the differences in smoke composition did not lead to relevant changes in the activity in in vitro or in vivo assays. The potential impact of using sugars as tobacco ingredients was further assessed in an indirect manner by comparing published data from markets with predominantly American-blend or Virginia-type (no added sugars) cigarettes. No relevant difference was found between these markets for smoking prevalence, intensity, some markers of dependence, nicotine uptake, or mortality from smoking-related lung cancer and chronic obstructive pulmonary disease. In conclusion, thorough examination of the data available suggests that the use of sugars as ingredients in cigarette tobacco does not increase the inherent risk and harm of cigarette smoking

Selection of sucrose concentration depends on the effort required to obtain it: studies using tetrabenazine, D₁, D₂, and D₃ receptor antagonists

RationaleLow doses of dopamine (DA) antagonists and accumbens DA depletions reduce food-reinforced instrumental behavior but do not impair primary food motivation, causing animals to reallocate behavior away from food-reinforced tasks with high response requirements and select less effortful alternatives. However, it is uncertain if this same pattern of effects would occur if sucrose was used as the reinforcer. Objectives These experiments studied the impact of DA depletion and antagonism on performance of an effort-related choice task using sucrose as the reinforcer, as well as sucrose consumption, preference, and taste reactivity tests. Methods The effects of DA manipulations were assessed using a task in which rats chose between lever pressing on a fixed ratio 7 schedule for 5.0 % sucrose versus freely consuming a less concentrated solution (0.3 %). Results The DA depleting agent tetrabenazine shifted effort-related choice, decreasing lever pressing for 5.0 % sucrose but increasing intake of the concurrently available 0.3 % sucrose. Tetrabenazine did not affect sucrose appetitive taste reactivity, or sucrose consumption or preference, in free consumption tests. The D1 antagonist ecopipam and the D2 antagonist haloperidol also shifted choice behavior at doses that did not alter sucrose consumption or preference. In contrast, sucrose pre-exposure reduced consumption across all conditions. D3 antagonism had no effects. Conclusions D1 and D2 receptor blockade and DA depletion reduce the tendency to work for sucrose under conditions that leave fundamental aspects of sucrose motivation (intake, preference, hedonic reactivity) intact. These findings have implications for studies employing sucrose intake or preference in animal models of depression