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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.

Randall PA, Lee CA, Podurgiel SJ, Hart E, Yohn SE, Jones M, Rowland M, López-Cruz L, Correa M, Salamone JD - Int. J. Neuropsychopharmacol. (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, University of Connecticut, Storrs, CT (Drs Randall, Lee, Podurgiel, Hart, Yohn, Jones, Rowland, Correa, and Salamone); Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC (Dr Randall); Department of Chemistry, North Carolina State University, NC (Dr Lee); Àrea de Psicobiologia, Campus de Riu Sec, Universitat Jaume I, Castelló, Spain (Drs López-Cruz and Correa).

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Top, DARPP-32 biochemistry in accumbens neurons containing dopamine (DA) D1 and D2 family receptors (see Bateup et al., 2008 for details). D1 receptor stimulation increases c-AMP production and protein kinase A (PKA) activity, which phosphorylates DARPP-32 to yield pDARPP-32(Thr34). D2 receptor stimulation decreases c-AMP production and protein kinase A activity, which decreases the dephosphorylation of pDARPP-32(Thr34) by protein phosphatase 2A (PP-2A), and therefore increases pDARPP-32(Thr75) expression. Bottom, High magnification photomicrographs of pDARPP-32(Thr34) (A) and pDARPP-32(Thr75) (B) staining in nucleus accumbens core, showing representative rats treated with 40.0mg/kg bupropion. Images were taken at 40× magnification. Scale bar=50 μm.
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Figure 3: Top, DARPP-32 biochemistry in accumbens neurons containing dopamine (DA) D1 and D2 family receptors (see Bateup et al., 2008 for details). D1 receptor stimulation increases c-AMP production and protein kinase A (PKA) activity, which phosphorylates DARPP-32 to yield pDARPP-32(Thr34). D2 receptor stimulation decreases c-AMP production and protein kinase A activity, which decreases the dephosphorylation of pDARPP-32(Thr34) by protein phosphatase 2A (PP-2A), and therefore increases pDARPP-32(Thr75) expression. Bottom, High magnification photomicrographs of pDARPP-32(Thr34) (A) and pDARPP-32(Thr75) (B) staining in nucleus accumbens core, showing representative rats treated with 40.0mg/kg bupropion. Images were taken at 40× magnification. Scale bar=50 μm.

Mentions: Figures 3 to 5 depict the effects of bupropion treatment on expression of pDARPP-32(Thr34) and pDARPP-32(Thr75) in accumbens core, accumbens shell, and overlying dorsal striatum (neostriatum). Bupropion increased signs of DA-related signal transduction at both D1 and D2 family receptors (Figures 3 and 4). ANOVA revealed a significant effect of drug treatment on pDARPP-32(Thr34) expression in accumbens core (F[2,12]=22.093, P<.05), shell (F[2,12]=12.862, P<.05), and dorsal striatum (F[2,12]=39.989, P<.05). Posthoc analysis (Tukey) revealed that pDARPP-32(Thr34) expression in the accumbens core was significantly increased at 20.0 and 40.0mg/kg (P<.05) compared with vehicle. These doses did not significantly differ from each other. In the accumbens shell and dorsal striatum, only 40.0mg/kg bupropion increased pDARPP-32(Thr34) expression over vehicle (P<.05). In addition, there was a significant effect of treatment on pDARPP-32(Thr75) expression in accumbens core (F[2,12]=4.191, P<.05), shell (F[2,12]=4.343, P<.05), and dorsal striatum (F[2,12]=5.473, P<.05). pDARPP-32(Thr75) expression in accumbens core, shell, and dorsal striatum was significantly increased by 40.0mg/kg bupropion (P<.05).


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.

Randall PA, Lee CA, Podurgiel SJ, Hart E, Yohn SE, Jones M, Rowland M, López-Cruz L, Correa M, Salamone JD - Int. J. Neuropsychopharmacol. (2014)

Top, DARPP-32 biochemistry in accumbens neurons containing dopamine (DA) D1 and D2 family receptors (see Bateup et al., 2008 for details). D1 receptor stimulation increases c-AMP production and protein kinase A (PKA) activity, which phosphorylates DARPP-32 to yield pDARPP-32(Thr34). D2 receptor stimulation decreases c-AMP production and protein kinase A activity, which decreases the dephosphorylation of pDARPP-32(Thr34) by protein phosphatase 2A (PP-2A), and therefore increases pDARPP-32(Thr75) expression. Bottom, High magnification photomicrographs of pDARPP-32(Thr34) (A) and pDARPP-32(Thr75) (B) staining in nucleus accumbens core, showing representative rats treated with 40.0mg/kg bupropion. Images were taken at 40× magnification. Scale bar=50 μm.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4368885&req=5

Figure 3: Top, DARPP-32 biochemistry in accumbens neurons containing dopamine (DA) D1 and D2 family receptors (see Bateup et al., 2008 for details). D1 receptor stimulation increases c-AMP production and protein kinase A (PKA) activity, which phosphorylates DARPP-32 to yield pDARPP-32(Thr34). D2 receptor stimulation decreases c-AMP production and protein kinase A activity, which decreases the dephosphorylation of pDARPP-32(Thr34) by protein phosphatase 2A (PP-2A), and therefore increases pDARPP-32(Thr75) expression. Bottom, High magnification photomicrographs of pDARPP-32(Thr34) (A) and pDARPP-32(Thr75) (B) staining in nucleus accumbens core, showing representative rats treated with 40.0mg/kg bupropion. Images were taken at 40× magnification. Scale bar=50 μm.
Mentions: Figures 3 to 5 depict the effects of bupropion treatment on expression of pDARPP-32(Thr34) and pDARPP-32(Thr75) in accumbens core, accumbens shell, and overlying dorsal striatum (neostriatum). Bupropion increased signs of DA-related signal transduction at both D1 and D2 family receptors (Figures 3 and 4). ANOVA revealed a significant effect of drug treatment on pDARPP-32(Thr34) expression in accumbens core (F[2,12]=22.093, P<.05), shell (F[2,12]=12.862, P<.05), and dorsal striatum (F[2,12]=39.989, P<.05). Posthoc analysis (Tukey) revealed that pDARPP-32(Thr34) expression in the accumbens core was significantly increased at 20.0 and 40.0mg/kg (P<.05) compared with vehicle. These doses did not significantly differ from each other. In the accumbens shell and dorsal striatum, only 40.0mg/kg bupropion increased pDARPP-32(Thr34) expression over vehicle (P<.05). In addition, there was a significant effect of treatment on pDARPP-32(Thr75) expression in accumbens core (F[2,12]=4.191, P<.05), shell (F[2,12]=4.343, P<.05), and dorsal striatum (F[2,12]=5.473, P<.05). pDARPP-32(Thr75) expression in accumbens core, shell, and dorsal striatum was significantly increased by 40.0mg/kg bupropion (P<.05).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, University of Connecticut, Storrs, CT (Drs Randall, Lee, Podurgiel, Hart, Yohn, Jones, Rowland, Correa, and Salamone); Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC (Dr Randall); Department of Chemistry, North Carolina State University, NC (Dr Lee); Àrea de Psicobiologia, Campus de Riu Sec, Universitat Jaume I, Castelló, Spain (Drs López-Cruz and Correa).

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Related in: MedlinePlus