Impact of Fluoxetine on Behavioral Invigoration of Appetitive and Aversively Motivated Responses: Interaction With Dopamine Depletion

Impaired behavioral activation and effort-related motivational dysfunctions like fatigue and anergia are debilitating treatment-resistant symptoms of depression. Depressed people show a bias towards the selection of low effort activities. To determine if the broadly used antidepressant fluoxetine can improve behavioral activation and reverse dopamine (DA) depletion-induced anergia, male CD1 mice were evaluated for vigorous escape behaviors in an aversive context (forced swim test, FST), and also with an exercise preference choice task [running wheel (RW)-T-maze choice task]. In the FST, fluoxetine increased active behaviors (swimming, climbing) while reducing passive ones (immobility). However, fluoxetine was not effective at reducing anergia induced by the DA-depleting agent tetrabenazine, further decreasing vigorous climbing and increasing immobility. In the T-maze, fluoxetine alone produced the same pattern of effects as tetrabenazine. Moreover, fluoxetine did not reverse tetrabenazine-induced suppression of RW time but it reduced sucrose intake duration. This pattern of effects produced by fluoxetine in DA-depleted mice was dissimilar from devaluing food reinforcement by pre-feeding or making the food bitter since in both cases sucrose intake time was reduced but animals compensated by increasing time in the RW. Thus, fluoxetine improved escape in an aversive context but decreased relative preference for active reinforcement. Moreover, fluoxetine did not reverse the anergic effects of DA depletion. These results have implications for the use of fluoxetine for treating motivational symptoms such as anergia in depressed patients

Preference for Exercise vs. More Sedentary Reinforcers: Validation of an Animal Model of Tetrabenazine-Induced Anergia

Physical activities can have intrinsic motivational or reinforcing properties. The choice to engage in voluntary physical activity is undertaken in relation to the selection of other alternatives, such as sedentary behaviors, drugs, or food intake. The mesolimbic dopamine (DA) system plays a critical role in behavioral activation or exertion of effort, and DA antagonism or depletion induces anergia in effort-based decision-making tasks. However, little is known about the neural mechanisms underlying the decision-making processes that establish preferences for sedentary vs. activity-based reinforcers. In the present work with male CD1 mice, we evaluated the effect of tetrabenazine (TBZ), a DA-depleting agent, on a three-choice T-maze task developed to assess preference between reinforcers with different behavioral activation requirements and sensory properties [i.e., a running wheel (RW) vs. sweet pellets or a neutral nonsocial odor]. We also studied the effects of TBZ on the forced swim test (FST), which measures climbing and swimming in a stressful setting, and on anxiety tests [dark-light (DL) box and elevated plus maze (EPM)]. In the three-choice task, TBZ reduced time running in the wheel but increased time spent consuming sucrose, thus indicating reduced activation but relatively intact sucrose reinforcement. The effect of TBZ was not mimicked by motivational manipulations that change the value of the reinforcers, such as making the RW aversive or harder to move, food-restricting the animals, inducing a binge-like eating pattern, or introducing social odors. In the FST, TBZ decreased time climbing (most active behavior) and increased immobility but did not affect anxiety in the DL or EPM. These results indicate that the three-choice T-maze task could be useful for assessing DA modulation of preferences for exercise based on activation and effort requirements, differentiating those effects from changes in preference produced by altering physical requirements, food restriction state, and stress during testing

Dopamine/adenosine interactions related to locomotion and tremor in animal models: Possible relevance to parkinsonism

Abstract Adenosine A 2A antagonists can exert antiparkinsonian effects in animal models. Recent experiments studied the ability of MSX-3 (an adenosine A 2A antagonist) to reverse the locomotor suppression and tremor produced by dopamine antagonists in rats. MSX-3 reversed haloperidolinduced suppression of locomotion, and reduced the tremulous jaw movements induced by haloperidol, pimozide, and reserpine. Infusions of MSX-3 into the nucleus accumbens core increased locomotion in haloperidol-treated rats, but there were no effects of infusions into the accumbens shell or ventrolateral neostriatum. In contrast, MSX-3 injected into the ventrolateral neostriatum reduced pimozide-induced tremulous jaw movements. Dopamine/adenosine interactions in different striatal subregions are involved in distinct aspects of motor function

Mecanismos neuroenzimáticos implicados en la regulación de las conductas inducidas por etanol: El papel de la catalasa cerebral

Manipulaciones farmacológicas para la regulación de la actividad del enzima catalasa y sus repercusiones en la locomoción y la narcosis inducidas por alcohol en ratones

Mecanismos neuroenzimáticos implicados en la regulación de las conductas inducidas por etanol: El papel de la catalasa cerebral

Manipulaciones farmacológicas para la regulación de la actividad del enzima catalasa y sus repercusiones en la locomoción y la narcosis inducidas por alcohol en ratones

Editorial: Ethanol, its active metabolites, and their mechanisms of action: Neurophysiological and behavioral effects

Ethanol, the main psychopharmacologically active ingredient of alcoholic drinks, represents a paradigmatic example of a research subject intrinsically able to perpetually self-generate interdisciplinary cutting-edge investigations.This eBook was inspired by the aim of providing an up-to-date characterization of the diverse effects of ethanol, of the possible mechanisms of action on different intracellular systems as well as of the hypothesized actions of ethanol and/or its metabolites on various neurotransmitters and neuromodulators.Indeed, the eBook provides a factual example of an excellent synthesis on the complex relationship between ethanol and its main biologically active metabolites (Chapter 1), on the behavioral and molecular consequences of early exposure to them (Chapter 2), on the recent proposals, advanced by the preclinical research, for new therapeutic approaches to distinct aspects of alcoholism (Chapter 3) and on the most recent and original preclinical evidence of the interactions between ethanol and/or its metabolites and the dopaminergic, adenosinergic and endocannabinoidergic systems (Chapter 4).Overall we believe that this eBook accomplishes its main goals of widening the perspective on this research subject and offering the readership a newer and, simultaneously, up-to-date and comprehensive scenery on ethanol’s and ethanol's active metabolites neurophysiological and behavioral effects

Mesolimbic Dopamine and the Regulation of Motivated Behavior

It has been known for some time that nucleus accumbens dopamine (DA) is involved in aspects of motivation , but theoretical approaches to understanding the functions of DA have continued to evolve based upon emerging data and novel concepts. Although it has become traditional to label DA neurons as “reward” neurons, the actual findings are more complicated than that, because they indicate that DA neurons can respond to a variety of motivationally significant stimuli. Moreover, it is important to distinguish between aspects of motivation that are differentially affected by dopaminergic manipulations. Studies that involve nucleus accumbens DA antagonism or depletion indicate that accumbens DA does not mediate primary food motivation or appetite. Nevertheless, DA is involved in appetitive and aversive motivational processes including behavioral activation , exertion of effort, sustained task engagement, and Pavlovian-to-instrumental transfer. Interference with accumbens DA transmission affects instrumental behavior in a manner that interacts with the response requirements of the task and also shifts effort-related choice behavior, biasing animals toward low-effort alternatives. Dysfunctions of mesolimbic DA may contribute to motivational symptoms seen in various psychopathologies, including depression , schizophrenia, parkinsonism, and other disorders

Dopamine depletion shifts behavior from activity based reinforcers to more sedentary ones and adenosine receptor antagonism reverses that shift: Relation to ventral striatum DARPP32 phosphorylation patterns

The mesolimbic dopamine (DA) system plays a critical role in behavioral activation and effort-based decision-making. DA depletion produces anergia (shifts to low effort options) in animals tested on effort-based decision-making tasks. Caffeine, the most consumed stimulant in the world, acts as an adenosine A1/A2A receptor antagonist, and in striatal areas DA D1 and D2 receptors are co-localized with adenosine A1 and A2A receptors respectively. In the present work, we evaluated the effect of caffeine on anergia induced by the VMAT-2 inhibitor tetrabenazine (TBZ), which depletes DA. Anergia was evaluated in a three-chamber T-maze task in which animals can chose between running on a wheel (RW) vs. sedentary activities such as consuming sucrose or sniffing a neutral odor. TBZ-caffeine interactions in ventral striatum were evaluated using DARPP-32 phosphorylation patterns as an intracellular marker of DA-adenosine receptor interaction. In the T-maze, control mice spent more time running and much less consuming sucrose or sniffing. TBZ (4.0 mg/kg) reduced ventral striatal DA tissue levels as measured by HPLC, and also shifted preferences in the T-maze, reducing selection of the reinforcer that involved vigorous activity (RW), but increasing consumption of a reinforcer that required little effort (sucrose), at doses that had no effect on independent measures of appetite or locomotion in a RW. Caffeine at doses that had no effect on their own reversed the effects of TBZ on T-maze performance, and also suppressed TBZ-induced pDARPP-32(Thr34) expression as measured by western blot, suggesting a role for D2-A2A interactions. These results support the idea that DA depletion produces anergia, but does not affect the primary motivational effects of sucrose. Caffeine, possibly by acting on A2A receptors in ventral striatum, reversed the DA depletion effects. It is possible that caffeine, like selective adenosine A2A antagonists, could have some therapeutic benefit for treating effort-related symptoms

The development of Digital Teaching Competence in Higher Education. A systematic review of the literature

El presente artículo tiene como objetivo presentar los resultados de una Revisión Sistemática de Literatura sobre los niveles de desarrollo de la Competencia Digital Docente en Educación Superior. Se procedió a seleccionar artículos tomando como base criterios de inclusión, eventos de interés y palabras clave, empleadas en los motores de búsqueda de tres bases de datos: Redalyc, Scopus y ERIC, incluyendo estudios en español y en inglés realizados entre los años 2015 y 2021. Se trabajó a través de una metodología que dividió el proceso en cuatro etapas en las cuales se realizó una minuciosa selección de artículos, empleando la Rúbrica COMDID y la Declaración PRISMA 2020. Basados en esta modalidad, se describieron hallazgos y niveles de desarrollo de la CDD, lo cual posibilitó la obtención de resultados de la revisión en función de las dimensiones e indicadores de la Rúbrica COMDID para los 47 artículos seleccionados. Se identificaron relatos de experiencias con TIC describiendo un escenario ideal, pero donde no se concretan los niveles más altos en el desarrollo de la CDD, y sin intervención didáctica en las prácticas educativas institucionales de los docentes, para los niveles expertos o transformadores.This article aims to present the results of a Systematic Literature Review on the level development of Teaching Digital Competence in Higher Education. Articles were selected based on inclusion criteria, events of interest and keywords, used in the search engines of three databases: Redalyc, Scopus and ERIC, including studies in Spanish and English carried out between 2015 and 2015. 2021. We worked through a methodology that divided the process into four stages in which a thorough selection of articles was carried out, using the COMDID Rubric and the PRISMA 2020. Through this methodology, findings and levels of development of the CDD were described, which made it possible to obtain the results of the review based on the dimensions and indicators of the COMDID Rubric for the 47 selected articles. Reports of experiences with ICT were identified, describing an ideal scenario, but where the highest levels in the development of CDD are not materialized, and without didactic intervention in the institutional educational practices of teachers at the expert or transformative levels