The adenosine A2A antagonist MSX-3 reverses the effects of the dopamine antagonist haloperidol on effort-related decision making in a T-maze cost/benefit procedure

• Published in: Psychopharmacologia 2009-05, Vol.204 (1), p.103-112
• Main Authors: Mott, Allison M., Nunes, Eric J., Collins, Lyndsey E., Port, Russell G., Sink, Kelly S., Hockemeyer, Jörg, Müller, Christa E., Salamone, John D.
• Format: Article
• Language: English
• Subjects: Adenosine A1 Receptor Antagonists; Adenosine A2 Receptor Antagonists; Animal behavior; Animal cognition; Animals; Antagonist drugs; Behavior, Animal - drug effects; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Choice Behavior - drug effects; Conditioning, Operant - drug effects; Dopamine Antagonists - pharmacology; Dose-Response Relationship, Drug; Drug Interactions; Haloperidol - pharmacology; Male; Maze Learning - physiology; Medical sciences; Motivation; Motor ability; Neuropharmacology; Neurosciences; Nucleus Accumbens - drug effects; Original Investigation; Pharmacology. Drug treatments; Pharmacology/Toxicology; Physical Exertion - drug effects; Psychiatry; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychomotor Performance - drug effects; Psychopharmacology; Psychotropic drugs; Rats; Rats, Sprague-Dawley; Receptor, Adenosine A1 - metabolism; Receptors, Adenosine A2 - metabolism; Reinforcement Schedule; Rodents; Xanthines - pharmacology
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-008-1441-z

Rationale Mesolimbic dopamine (DA) is a critical component of the brain circuitry regulating behavioral activation and effort-related processes. Research involving choice tasks has shown that rats with impaired DA transmission reallocate their instrumental behavior away from food-reinforced tasks with high response requirements and instead select less effortful food-seeking behaviors. Objective Previous work showed that adenosine A 2A antagonism can reverse the effects of the DA antagonist haloperidol in an operant task that assesses effort-related choice. The present work used a T-maze choice procedure to assess the effects of adenosine A 2A and A 1 antagonism. Materials and methods With this task, the two arms of the maze have different reinforcement densities (four vs. two food pellets), and a vertical 44 cm barrier is positioned in the arm with the higher density, presenting the animal with an effort-related challenge. Untreated rats strongly prefer the arm with the high density of food reward and climb the barrier in order to obtain the food. Results Haloperidol produced a dose-related (0.05–0.15 mg/kg i.p.) reduction in the number of trials in which the rats chose the high-barrier arm. Co-administration of the adenosine A 2A receptor antagonist MSX-3 (0.75, 1.5, and 3.0 mg/kg i.p.), but not the A 1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (0.75, 1.5, and 3.0 mg/kg i.p.), reversed the effects of haloperidol on effort-related choice and latency. Conclusions Adenosine A 2A and D2 receptors interact to regulate effort-related decision making, which may have implications for the treatment of psychiatric symptoms such as psychomotor slowing or anergia that can be observed in depression, parkinsonism, and other disorders.