The Experts below are selected from a list of 2010 Experts worldwide ranked by ideXlab platform
John D. Salamone - One of the best experts on this subject based on the ideXlab platform.
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evaluation of the effort related motivational effects of the novel dopamine Uptake inhibitor prx 14040
Pharmacology Biochemistry and Behavior, 2016Co-Authors: Samantha E. Yohn, Mercè Correa, Laura Lopezcruz, Augustyna Gogoj, Aileen Haque, Allison Haley, Philip Huxley, Patricia Baskin, John D. SalamoneAbstract:Psychiatric disorders are often marked by effort-related motivational symptoms such as anergia, fatigue, psychomotor retardation, and alterations in effort-based decision making. Animal studies of effort-related choice behavior are being used to model these symptoms. With these procedures, animals are offered a choice between high effort instrumental actions leading to highly valued reinforcers vs. low effort/low reward options. In the present experiments the motivational effects of a novel dopamine (DA) Uptake inhibitor, PRX-14040 (PRX), were assessed using tests of effort-based choice in rats. For the two experiments, rats were tested using the concurrent fixed ratio 5 (FR5)/chow feeding choice task. In the first 2 experiments, the vesicular monoamine transport (VMAT-2) inhibitor tetrabenazine (TBZ), which blocks DA storage and depletes DA, was used to produce a shift in effort-related choice, decreasing lever pressing and increasing chow intake. Co-administration of PRX reversed the effects of TBZ, increasing lever pressing and decreasing chow intake in TBZ-treated rats. In experiment 2, PRX was compared with the Catecholamine Uptake inhibitor and antidepressant bupropion (Wellbutrin), the stimulant drug methylphenidate, and the wakefulness agent modafinil. All four drugs reversed the effects of TBZ, and PRX compared favorably with these compounds. In the final experiment, PRX was assessed for its ability to increase work output in rats responding on a progressive ratio (PROG)/chow feeding choice task in rats that were otherwise untreated. PRX biased animals towards greater exertion of effort, increasing PROG lever pressing output while decreasing chow intake. In summary, PRX was able to reverse the effects of TBZ, and to increase selection of high effort activities. Taken together, these results suggest that PRX could be useful as a treatment for effort-related motivational dysfunction in humans.
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bupropion increases selection of high effort activity in rats tested on a progressive ratio chow feeding choice procedure implications for treatment of effort related motivational symptoms
The International Journal of Neuropsychopharmacology, 2015Co-Authors: Patrick A. Randall, Samantha E. Yohn, Christie A. Lee, Mercè Correa, Samantha J Podurgiel, Evan E Hart, Myles Jones, Margaret Rowland, Laura Lopezcruz, John D. SalamoneAbstract:Background: Depression and related disorders are characterized by deficits in behavioral activation, exertion of effort, and other psychomotor/motivational dysfunctions. Depressed patients show alterations in effort-related decision making and a bias towards selection of low effort activities. It has been suggested that animal tests of effort-related decision making could be useful as models of motivational dysfunctions seen in psychopathology. Methods: Because clinical studies have suggested that inhibition of Catecholamine Uptake may be a useful strategy for treatment of effort-related motivational symptoms, the present research assessed the ability of bupropion to increase work output in rats responding on a test of effort-related decision-making (ie, a progressive ratio/chow feeding choice task). With this task, rats can choose between working for a preferred food (high-carbohydrate pellets) by lever pressing on a progressive ratio schedule vs obtaining a less preferred laboratory chow that is freely available in the chamber. Results: Bupropion (10.0–40.0 mg/kg intraperitoneal) significantly increased all measures of progressive ratio lever pressing, but decreased chow intake. These effects were greatest in animals with low baseline levels of work output on the progressive ratio schedule. Because accumbens dopamine is implicated in effort-related processes, the effects of bupropion on markers of accumbens dopamine transmission were examined. Bupropion elevated extracellular dopamine levels in accumbens core as measured by microdialysis and increased phosphorylated dopamine and cyclic-AMP related phosphoprotein 32 kDaltons (pDARPP-32) immunoreactivity in a manner consistent with D1 and D2 receptor stimulation. Conclusion: The ability of bupropion to increase exertion of effort in instrumental behavior may have implications for the pathophysiology and treatment of effort-related motivational symptoms in humans.
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The VMAT-2 inhibitor tetrabenazine alters effort-related decision making as measured by the T-maze barrier choice task: reversal with the adenosine A2A antagonist MSX-3 and the Catecholamine Uptake blocker bupropion.
Psychopharmacology, 2014Co-Authors: Samantha E. Yohn, Christian Thompson, Patrick A. Randall, Christie A. Lee, Christa E. Müller, Younis Baqi, Mercè Correa, John D. SalamoneAbstract:Rationale Depressed people show effort-related motivational symptoms, such as anergia, retardation, lassitude, and fatigue. Animal tests can model these motivational symptoms, and the present studies characterized the effort-related effects of the vesicular monoamine transport (VMAT-2) inhibitor tetrabenazine. Tetrabenazine produces depressive symptoms in humans and, at low doses, preferentially depletes dopamine.
Samantha E. Yohn - One of the best experts on this subject based on the ideXlab platform.
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evaluation of the effort related motivational effects of the novel dopamine Uptake inhibitor prx 14040
Pharmacology Biochemistry and Behavior, 2016Co-Authors: Samantha E. Yohn, Mercè Correa, Laura Lopezcruz, Augustyna Gogoj, Aileen Haque, Allison Haley, Philip Huxley, Patricia Baskin, John D. SalamoneAbstract:Psychiatric disorders are often marked by effort-related motivational symptoms such as anergia, fatigue, psychomotor retardation, and alterations in effort-based decision making. Animal studies of effort-related choice behavior are being used to model these symptoms. With these procedures, animals are offered a choice between high effort instrumental actions leading to highly valued reinforcers vs. low effort/low reward options. In the present experiments the motivational effects of a novel dopamine (DA) Uptake inhibitor, PRX-14040 (PRX), were assessed using tests of effort-based choice in rats. For the two experiments, rats were tested using the concurrent fixed ratio 5 (FR5)/chow feeding choice task. In the first 2 experiments, the vesicular monoamine transport (VMAT-2) inhibitor tetrabenazine (TBZ), which blocks DA storage and depletes DA, was used to produce a shift in effort-related choice, decreasing lever pressing and increasing chow intake. Co-administration of PRX reversed the effects of TBZ, increasing lever pressing and decreasing chow intake in TBZ-treated rats. In experiment 2, PRX was compared with the Catecholamine Uptake inhibitor and antidepressant bupropion (Wellbutrin), the stimulant drug methylphenidate, and the wakefulness agent modafinil. All four drugs reversed the effects of TBZ, and PRX compared favorably with these compounds. In the final experiment, PRX was assessed for its ability to increase work output in rats responding on a progressive ratio (PROG)/chow feeding choice task in rats that were otherwise untreated. PRX biased animals towards greater exertion of effort, increasing PROG lever pressing output while decreasing chow intake. In summary, PRX was able to reverse the effects of TBZ, and to increase selection of high effort activities. Taken together, these results suggest that PRX could be useful as a treatment for effort-related motivational dysfunction in humans.
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bupropion increases selection of high effort activity in rats tested on a progressive ratio chow feeding choice procedure implications for treatment of effort related motivational symptoms
The International Journal of Neuropsychopharmacology, 2015Co-Authors: Patrick A. Randall, Samantha E. Yohn, Christie A. Lee, Mercè Correa, Samantha J Podurgiel, Evan E Hart, Myles Jones, Margaret Rowland, Laura Lopezcruz, John D. SalamoneAbstract:Background: Depression and related disorders are characterized by deficits in behavioral activation, exertion of effort, and other psychomotor/motivational dysfunctions. Depressed patients show alterations in effort-related decision making and a bias towards selection of low effort activities. It has been suggested that animal tests of effort-related decision making could be useful as models of motivational dysfunctions seen in psychopathology. Methods: Because clinical studies have suggested that inhibition of Catecholamine Uptake may be a useful strategy for treatment of effort-related motivational symptoms, the present research assessed the ability of bupropion to increase work output in rats responding on a test of effort-related decision-making (ie, a progressive ratio/chow feeding choice task). With this task, rats can choose between working for a preferred food (high-carbohydrate pellets) by lever pressing on a progressive ratio schedule vs obtaining a less preferred laboratory chow that is freely available in the chamber. Results: Bupropion (10.0–40.0 mg/kg intraperitoneal) significantly increased all measures of progressive ratio lever pressing, but decreased chow intake. These effects were greatest in animals with low baseline levels of work output on the progressive ratio schedule. Because accumbens dopamine is implicated in effort-related processes, the effects of bupropion on markers of accumbens dopamine transmission were examined. Bupropion elevated extracellular dopamine levels in accumbens core as measured by microdialysis and increased phosphorylated dopamine and cyclic-AMP related phosphoprotein 32 kDaltons (pDARPP-32) immunoreactivity in a manner consistent with D1 and D2 receptor stimulation. Conclusion: The ability of bupropion to increase exertion of effort in instrumental behavior may have implications for the pathophysiology and treatment of effort-related motivational symptoms in humans.
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The VMAT-2 inhibitor tetrabenazine alters effort-related decision making as measured by the T-maze barrier choice task: reversal with the adenosine A2A antagonist MSX-3 and the Catecholamine Uptake blocker bupropion.
Psychopharmacology, 2014Co-Authors: Samantha E. Yohn, Christian Thompson, Patrick A. Randall, Christie A. Lee, Christa E. Müller, Younis Baqi, Mercè Correa, John D. SalamoneAbstract:Rationale Depressed people show effort-related motivational symptoms, such as anergia, retardation, lassitude, and fatigue. Animal tests can model these motivational symptoms, and the present studies characterized the effort-related effects of the vesicular monoamine transport (VMAT-2) inhibitor tetrabenazine. Tetrabenazine produces depressive symptoms in humans and, at low doses, preferentially depletes dopamine.
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the vmat 2 inhibitor tetrabenazine affects effort related decision making in a progressive ratio chow feeding choice task reversal with antidepressant drugs
PLOS ONE, 2014Co-Authors: Patrick A. Randall, Samantha E. Yohn, Christie A. Lee, Eric J Nunes, Victoria Nowak, Bilal Khan, Priya Shah, Saagar Pandit, Kiran V Vemuri, Alexandros MakriyannisAbstract:Behavioral activation is a fundamental feature of motivation, and organisms frequently make effort-related decisions based upon evaluations of reinforcement value and response costs. Furthermore, people with major depression and other disorders often show anergia, psychomotor retardation, fatigue, and alterations in effort-related decision making. Tasks measuring effort-based decision making can be used as animal models of the motivational symptoms of depression, and the present studies characterized the effort-related effects of the vesicular monoamine transport (VMAT-2) inhibitor tetrabenazine. Tetrabenazine induces depressive symptoms in humans, and also preferentially depletes dopamine (DA). Rats were assessed using a concurrent progressive ratio (PROG)/chow feeding task, in which they can either lever press on a PROG schedule for preferred high-carbohydrate food, or approach and consume a less-preferred lab chow that is freely available in the chamber. Previous work has shown that the DA antagonist haloperidol reduced PROG work output on this task, but did not reduce chow intake, effects that differed substantially from those of reinforcer devaluation or appetite suppressant drugs. The present work demonstrated that tetrabenazine produced an effort-related shift in responding on the PROG/chow procedure, reducing lever presses, highest ratio achieved and time spent responding, but not reducing chow intake. Similar effects were produced by administration of the subtype selective DA antagonists ecopipam (D1) and eticlopride (D2), but not by the cannabinoid CB1 receptor neutral antagonist and putative appetite suppressant AM 4413, which suppressed both lever pressing and chow intake. The adenosine A2A antagonist MSX-3, the antidepressant and Catecholamine Uptake inhibitor bupropion, and the MAO-B inhibitor deprenyl, all reversed the impairments induced by tetrabenazine. This work demonstrates the potential utility of the PROG/chow procedure as a rodent model of the effort-related deficits observed in depressed patients.
Nazareno Paolocci - One of the best experts on this subject based on the ideXlab platform.
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cholinergic neurons of mouse intrinsic cardiac ganglia contain noradrenergic enzymes norepinephrine transporters and the neurotrophin receptors tropomyosin related kinase a and p75
Neuroscience, 2008Co-Authors: Jennifer L Hoard, Abigail M Mabe, Donald B Hoover, Randy D Blakely, Ning Feng, Nazareno PaolocciAbstract:Abstract Half of the cholinergic neurons of human and primate intrinsic cardiac ganglia (ICG) have a dual cholinergic/noradrenergic phenotype. Likewise, a large subpopulation of cholinergic neurons of the mouse heart expresses enzymes needed for synthesis of norepinephrine (NE), but they lack the vesicular monoamine transporter type 2 (VMAT2) required for Catecholamine storage. In the present study, we determined the full scope of noradrenergic properties (i.e. synthetic enzymes and transporters) expressed by cholinergic neurons of mouse ICG, estimated the relative abundance of neurons expressing different elements of the noradrenergic phenotype, and evaluated the colocalization of cholinergic and noradrenergic markers in atrial nerve fibers. Stellate ganglia were used as a positive control for noradrenergic markers. Using fluorescence immunohistochemistry and confocal microscopy, we found that about 30% of cholinergic cell bodies contained tyrosine hydroxylase (TH), including the activated form that is phosphorylated at Ser-40 (pSer40 TH). Dopamine β-hydroxylase (DBH) and norepinephrine transporter (NET) were present in all cholinergic somata, indicating a wider capability for dopamine metabolism and Catecholamine Uptake. Yet, cholinergic somata lacked VMAT2, precluding the potential for NE storage and vesicular release. In contrast to cholinergic somata, cardiac nerve fibers rarely showed colocalization of cholinergic and noradrenergic markers. Instead, these labels were closely apposed but clearly distinct from each other. Since cholinergic somata expressed several noradrenergic proteins, we questioned whether these neurons might also contain trophic factor receptors typical of noradrenergic neurons. Indeed, we found that all cholinergic cell bodies of mouse ICG, like noradrenergic cell bodies of the stellate ganglia, contained both tropomyosin-related kinase A (TrkA) and p75 neurotrophin receptors. Collectively, these findings demonstrate that mouse intrinsic cardiac neurons (ICNs), like those of humans, have a complex neurochemical phenotype that goes beyond the classical view of cardiac parasympathetic neurons. They also suggest that neurotrophins and local NE synthesis might have important effects on neurons of the mouse ICG.
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cholinergic neurons of mouse intrinsic cardiac ganglia contain noradrenergic enzymes norepinephrine transporters and the neurotrophin receptors tropomyosin related kinase a and p75
Neuroscience, 2008Co-Authors: Jennifer L Hoard, Abigail M Mabe, Donald B Hoover, Randy D Blakely, Ning Feng, Nazareno PaolocciAbstract:Half of the cholinergic neurons of human and primate intrinsic cardiac ganglia (ICG) have a dual cholinergic/noradrenergic phenotype. Likewise, a large subpopulation of cholinergic neurons of the mouse heart expresses enzymes needed for synthesis of norepinephrine (NE), but they lack the vesicular monoamine transporter type 2 (VMAT2) required for Catecholamine storage. In the present study, we determined the full scope of noradrenergic properties (i.e. synthetic enzymes and transporters) expressed by cholinergic neurons of mouse ICG, estimated the relative abundance of neurons expressing different elements of the noradrenergic phenotype, and evaluated the colocalization of cholinergic and noradrenergic markers in atrial nerve fibers. Stellate ganglia were used as a positive control for noradrenergic markers. Using fluorescence immunohistochemistry and confocal microscopy, we found that about 30% of cholinergic cell bodies contained tyrosine hydroxylase (TH), including the activated form that is phosphorylated at Ser-40 (pSer40 TH). Dopamine beta-hydroxylase (DBH) and norepinephrine transporter (NET) were present in all cholinergic somata, indicating a wider capability for dopamine metabolism and Catecholamine Uptake. Yet, cholinergic somata lacked VMAT2, precluding the potential for NE storage and vesicular release. In contrast to cholinergic somata, cardiac nerve fibers rarely showed colocalization of cholinergic and noradrenergic markers. Instead, these labels were closely apposed but clearly distinct from each other. Since cholinergic somata expressed several noradrenergic proteins, we questioned whether these neurons might also contain trophic factor receptors typical of noradrenergic neurons. Indeed, we found that all cholinergic cell bodies of mouse ICG, like noradrenergic cell bodies of the stellate ganglia, contained both tropomyosin-related kinase A (TrkA) and p75 neurotrophin receptors. Collectively, these findings demonstrate that mouse intrinsic cardiac neurons (ICNs), like those of humans, have a complex neurochemical phenotype that goes beyond the classical view of cardiac parasympathetic neurons. They also suggest that neurotrophins and local NE synthesis might have important effects on neurons of the mouse ICG.
Patrick A. Randall - One of the best experts on this subject based on the ideXlab platform.
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bupropion increases selection of high effort activity in rats tested on a progressive ratio chow feeding choice procedure implications for treatment of effort related motivational symptoms
The International Journal of Neuropsychopharmacology, 2015Co-Authors: Patrick A. Randall, Samantha E. Yohn, Christie A. Lee, Mercè Correa, Samantha J Podurgiel, Evan E Hart, Myles Jones, Margaret Rowland, Laura Lopezcruz, John D. SalamoneAbstract:Background: Depression and related disorders are characterized by deficits in behavioral activation, exertion of effort, and other psychomotor/motivational dysfunctions. Depressed patients show alterations in effort-related decision making and a bias towards selection of low effort activities. It has been suggested that animal tests of effort-related decision making could be useful as models of motivational dysfunctions seen in psychopathology. Methods: Because clinical studies have suggested that inhibition of Catecholamine Uptake may be a useful strategy for treatment of effort-related motivational symptoms, the present research assessed the ability of bupropion to increase work output in rats responding on a test of effort-related decision-making (ie, a progressive ratio/chow feeding choice task). With this task, rats can choose between working for a preferred food (high-carbohydrate pellets) by lever pressing on a progressive ratio schedule vs obtaining a less preferred laboratory chow that is freely available in the chamber. Results: Bupropion (10.0–40.0 mg/kg intraperitoneal) significantly increased all measures of progressive ratio lever pressing, but decreased chow intake. These effects were greatest in animals with low baseline levels of work output on the progressive ratio schedule. Because accumbens dopamine is implicated in effort-related processes, the effects of bupropion on markers of accumbens dopamine transmission were examined. Bupropion elevated extracellular dopamine levels in accumbens core as measured by microdialysis and increased phosphorylated dopamine and cyclic-AMP related phosphoprotein 32 kDaltons (pDARPP-32) immunoreactivity in a manner consistent with D1 and D2 receptor stimulation. Conclusion: The ability of bupropion to increase exertion of effort in instrumental behavior may have implications for the pathophysiology and treatment of effort-related motivational symptoms in humans.
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The VMAT-2 inhibitor tetrabenazine alters effort-related decision making as measured by the T-maze barrier choice task: reversal with the adenosine A2A antagonist MSX-3 and the Catecholamine Uptake blocker bupropion.
Psychopharmacology, 2014Co-Authors: Samantha E. Yohn, Christian Thompson, Patrick A. Randall, Christie A. Lee, Christa E. Müller, Younis Baqi, Mercè Correa, John D. SalamoneAbstract:Rationale Depressed people show effort-related motivational symptoms, such as anergia, retardation, lassitude, and fatigue. Animal tests can model these motivational symptoms, and the present studies characterized the effort-related effects of the vesicular monoamine transport (VMAT-2) inhibitor tetrabenazine. Tetrabenazine produces depressive symptoms in humans and, at low doses, preferentially depletes dopamine.
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the vmat 2 inhibitor tetrabenazine affects effort related decision making in a progressive ratio chow feeding choice task reversal with antidepressant drugs
PLOS ONE, 2014Co-Authors: Patrick A. Randall, Samantha E. Yohn, Christie A. Lee, Eric J Nunes, Victoria Nowak, Bilal Khan, Priya Shah, Saagar Pandit, Kiran V Vemuri, Alexandros MakriyannisAbstract:Behavioral activation is a fundamental feature of motivation, and organisms frequently make effort-related decisions based upon evaluations of reinforcement value and response costs. Furthermore, people with major depression and other disorders often show anergia, psychomotor retardation, fatigue, and alterations in effort-related decision making. Tasks measuring effort-based decision making can be used as animal models of the motivational symptoms of depression, and the present studies characterized the effort-related effects of the vesicular monoamine transport (VMAT-2) inhibitor tetrabenazine. Tetrabenazine induces depressive symptoms in humans, and also preferentially depletes dopamine (DA). Rats were assessed using a concurrent progressive ratio (PROG)/chow feeding task, in which they can either lever press on a PROG schedule for preferred high-carbohydrate food, or approach and consume a less-preferred lab chow that is freely available in the chamber. Previous work has shown that the DA antagonist haloperidol reduced PROG work output on this task, but did not reduce chow intake, effects that differed substantially from those of reinforcer devaluation or appetite suppressant drugs. The present work demonstrated that tetrabenazine produced an effort-related shift in responding on the PROG/chow procedure, reducing lever presses, highest ratio achieved and time spent responding, but not reducing chow intake. Similar effects were produced by administration of the subtype selective DA antagonists ecopipam (D1) and eticlopride (D2), but not by the cannabinoid CB1 receptor neutral antagonist and putative appetite suppressant AM 4413, which suppressed both lever pressing and chow intake. The adenosine A2A antagonist MSX-3, the antidepressant and Catecholamine Uptake inhibitor bupropion, and the MAO-B inhibitor deprenyl, all reversed the impairments induced by tetrabenazine. This work demonstrates the potential utility of the PROG/chow procedure as a rodent model of the effort-related deficits observed in depressed patients.
Mercè Correa - One of the best experts on this subject based on the ideXlab platform.
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evaluation of the effort related motivational effects of the novel dopamine Uptake inhibitor prx 14040
Pharmacology Biochemistry and Behavior, 2016Co-Authors: Samantha E. Yohn, Mercè Correa, Laura Lopezcruz, Augustyna Gogoj, Aileen Haque, Allison Haley, Philip Huxley, Patricia Baskin, John D. SalamoneAbstract:Psychiatric disorders are often marked by effort-related motivational symptoms such as anergia, fatigue, psychomotor retardation, and alterations in effort-based decision making. Animal studies of effort-related choice behavior are being used to model these symptoms. With these procedures, animals are offered a choice between high effort instrumental actions leading to highly valued reinforcers vs. low effort/low reward options. In the present experiments the motivational effects of a novel dopamine (DA) Uptake inhibitor, PRX-14040 (PRX), were assessed using tests of effort-based choice in rats. For the two experiments, rats were tested using the concurrent fixed ratio 5 (FR5)/chow feeding choice task. In the first 2 experiments, the vesicular monoamine transport (VMAT-2) inhibitor tetrabenazine (TBZ), which blocks DA storage and depletes DA, was used to produce a shift in effort-related choice, decreasing lever pressing and increasing chow intake. Co-administration of PRX reversed the effects of TBZ, increasing lever pressing and decreasing chow intake in TBZ-treated rats. In experiment 2, PRX was compared with the Catecholamine Uptake inhibitor and antidepressant bupropion (Wellbutrin), the stimulant drug methylphenidate, and the wakefulness agent modafinil. All four drugs reversed the effects of TBZ, and PRX compared favorably with these compounds. In the final experiment, PRX was assessed for its ability to increase work output in rats responding on a progressive ratio (PROG)/chow feeding choice task in rats that were otherwise untreated. PRX biased animals towards greater exertion of effort, increasing PROG lever pressing output while decreasing chow intake. In summary, PRX was able to reverse the effects of TBZ, and to increase selection of high effort activities. Taken together, these results suggest that PRX could be useful as a treatment for effort-related motivational dysfunction in humans.
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bupropion increases selection of high effort activity in rats tested on a progressive ratio chow feeding choice procedure implications for treatment of effort related motivational symptoms
The International Journal of Neuropsychopharmacology, 2015Co-Authors: Patrick A. Randall, Samantha E. Yohn, Christie A. Lee, Mercè Correa, Samantha J Podurgiel, Evan E Hart, Myles Jones, Margaret Rowland, Laura Lopezcruz, John D. SalamoneAbstract:Background: Depression and related disorders are characterized by deficits in behavioral activation, exertion of effort, and other psychomotor/motivational dysfunctions. Depressed patients show alterations in effort-related decision making and a bias towards selection of low effort activities. It has been suggested that animal tests of effort-related decision making could be useful as models of motivational dysfunctions seen in psychopathology. Methods: Because clinical studies have suggested that inhibition of Catecholamine Uptake may be a useful strategy for treatment of effort-related motivational symptoms, the present research assessed the ability of bupropion to increase work output in rats responding on a test of effort-related decision-making (ie, a progressive ratio/chow feeding choice task). With this task, rats can choose between working for a preferred food (high-carbohydrate pellets) by lever pressing on a progressive ratio schedule vs obtaining a less preferred laboratory chow that is freely available in the chamber. Results: Bupropion (10.0–40.0 mg/kg intraperitoneal) significantly increased all measures of progressive ratio lever pressing, but decreased chow intake. These effects were greatest in animals with low baseline levels of work output on the progressive ratio schedule. Because accumbens dopamine is implicated in effort-related processes, the effects of bupropion on markers of accumbens dopamine transmission were examined. Bupropion elevated extracellular dopamine levels in accumbens core as measured by microdialysis and increased phosphorylated dopamine and cyclic-AMP related phosphoprotein 32 kDaltons (pDARPP-32) immunoreactivity in a manner consistent with D1 and D2 receptor stimulation. Conclusion: The ability of bupropion to increase exertion of effort in instrumental behavior may have implications for the pathophysiology and treatment of effort-related motivational symptoms in humans.
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The VMAT-2 inhibitor tetrabenazine alters effort-related decision making as measured by the T-maze barrier choice task: reversal with the adenosine A2A antagonist MSX-3 and the Catecholamine Uptake blocker bupropion.
Psychopharmacology, 2014Co-Authors: Samantha E. Yohn, Christian Thompson, Patrick A. Randall, Christie A. Lee, Christa E. Müller, Younis Baqi, Mercè Correa, John D. SalamoneAbstract:Rationale Depressed people show effort-related motivational symptoms, such as anergia, retardation, lassitude, and fatigue. Animal tests can model these motivational symptoms, and the present studies characterized the effort-related effects of the vesicular monoamine transport (VMAT-2) inhibitor tetrabenazine. Tetrabenazine produces depressive symptoms in humans and, at low doses, preferentially depletes dopamine.