RATIONALE: Organisms frequently make effort-related decisions based upon assessments of motivational value and response costs. Energy-related dysfunctions such as psychomotor slowing and apathy are critically involved in some clinical syndromes. Dopamine (DA), particularly in the nucleus accumbens, regulates effort-related processes. Dopamine antagonism and accumbens dopamine depletions cause rats performing on choice tasks to reallocate their behavior away from food-reinforced tasks that have high response requirements. OBJECTIVE: There is evidence of a functional interaction between DA and adenosine A(2A) receptors in the neostriatum and nucleus accumbens. The present experiments were conducted to determine if adenosine A(2A) receptor antagonism could reverse the effects of dopamine receptor antagonism on instrumental behavior and effort-related choice. MATERIALS AND METHODS: The adenosine A(2A) receptor antagonist MSX-3 was investigated for its ability to reverse the effects of the dopamine receptor antagonist haloperidol (0.1 mg/kg) on fixed ratio 5 instrumental lever-pressing and on response allocation using a concurrent lever-pressing/chow-feeding choice task. RESULTS: Haloperidol significantly suppressed fixed ratio 5 responding, and with rats responding on the concurrent choice task, it altered choice behavior, significantly reducing lever-pressing for food and increasing chow intake. Injections of MSX-3 (0.5-2.0 mg/kg) produced a dose-related attenuation of the effects of 0.1 mg/kg haloperidol on both tasks. The high dose of MSX-3, when administered in the absence of haloperidol, did not significantly affect responding on either task. CONCLUSIONS: Adenosine and dopamine systems interact to regulate instrumental behavior and effort-related processes, which may have implications for the treatment of psychiatric symptoms such as psychomotor slowing or anergia.
RATIONALE: Organisms frequently make effort-related decisions based upon assessments of motivational value and response costs. Energy-related dysfunctions such as psychomotor slowing and apathy are critically involved in some clinical syndromes. Dopamine (DA), particularly in the nucleus accumbens, regulates effort-related processes. Dopamine antagonism and accumbens dopamine depletions cause rats performing on choice tasks to reallocate their behavior away from food-reinforced tasks that have high response requirements. OBJECTIVE: There is evidence of a functional interaction between DA and adenosine A(2A) receptors in the neostriatum and nucleus accumbens. The present experiments were conducted to determine if adenosine A(2A) receptor antagonism could reverse the effects of dopamine receptor antagonism on instrumental behavior and effort-related choice. MATERIALS AND METHODS: The adenosine A(2A) receptor antagonist MSX-3 was investigated for its ability to reverse the effects of the dopamine receptor antagonist haloperidol (0.1 mg/kg) on fixed ratio 5 instrumental lever-pressing and on response allocation using a concurrent lever-pressing/chow-feeding choice task. RESULTS:Haloperidol significantly suppressed fixed ratio 5 responding, and with rats responding on the concurrent choice task, it altered choice behavior, significantly reducing lever-pressing for food and increasing chow intake. Injections of MSX-3 (0.5-2.0 mg/kg) produced a dose-related attenuation of the effects of 0.1 mg/kg haloperidol on both tasks. The high dose of MSX-3, when administered in the absence of haloperidol, did not significantly affect responding on either task. CONCLUSIONS:Adenosine and dopamine systems interact to regulate instrumental behavior and effort-related processes, which may have implications for the treatment of psychiatric symptoms such as psychomotor slowing or anergia.
Authors: F Denk; M E Walton; K A Jennings; T Sharp; M F S Rushworth; D M Bannerman Journal: Psychopharmacology (Berl) Date: 2004-12-10 Impact factor: 4.530
Authors: Keita Ishiwari; Lisa J Madson; Andrew M Farrar; Susana M Mingote; John P Valenta; Michael D DiGianvittorio; Lauren E Frank; Merce Correa; Jörg Hockemeyer; Christa Müller; John D Salamone Journal: Behav Brain Res Date: 2006-12-21 Impact factor: 3.332
Authors: John D Salamone; Andrew M Farrar; Laura Font; Vatsal Patel; Devra E Schlar; Eric J Nunes; Lyndsey E Collins; Thomas N Sager Journal: Behav Brain Res Date: 2009-03-03 Impact factor: 3.332
Authors: Irene Avila; Mark P Reilly; Federico Sanabria; Diana Posadas-Sánchez; Claudia L Chavez; Nikhil Banerjee; Peter Killeen; Eddie Castañeda Journal: Behav Brain Res Date: 2008-11-27 Impact factor: 3.332