Different function of pedunculopontine GABA and glutamate receptors in nucleus accumbens dopamine, pedunculopontine glutamate and operant discriminative behavior.
The nucleus accumbens, as the main input structure of the ventral basal ganglia loop, is described as a limbic-motor interface. Dopamine input to nucleus accumbens modulates processing of concurrent glutamate input from limbic structures carrying motor and motivational information. There is evidence that these dopamine/glutamate interactions are fundamentally involved in response selection processes. However, the pedunculopontine tegmental nucleus (PPTg) in the brainstem is connected with limbic structures as well as dopaminergic midbrain areas, which also project to the nucleus accumbens. Furthermore, behavioral studies implicate the PPTg in complex, motivated behavior. Thus, the PPTg might be involved in motivated behavior by influencing response selection processes in the nucleus accumbens. In this study we used in vivo microdialysis in freely moving rats in order to inhibit (100, 200, 300 and 400 microm baclofen) or stimulate [5, 12.5, 25 or 50 micromalpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA)] the PPTg in animals that are performing an operant discrimination task for food reward. The behavioral consequences were correlated with dopamine and glutamate levels in nucleus accumbens and PPTg, respectively. PPTg inhibition by local GABAB receptors impaired the response rate and accuracy of performance in the operant discrimination task. PPTg stimulation by local AMPA receptors exclusively impaired the response rate. Both treatments blocked the performance-driven dopamine signal in nucleus accumbens, whereas glutamate in PPTg was enhanced after AMPA administration only. The data indicate that the PPTg functionally participates in a network of subcortical and cortical structures, which is responsible for the execution of motivated behavior and response selection processes.
Steiniger-Brach
Björn
B
University of Tübingen, Department of Neuropharmacology, Tübingen, Germany. BSBR@Lundbeck.com
Kretschmer
Beate D
BD
D000704:Analysis of Variance; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001522:Behavior, Animal; D001923:Brain Chemistry; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology*; D004192:Discrimination, Psychological / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D008636:Mesencephalon / Q000502:physiology*; D017551:Microdialysis / Q000379:methods; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000502:physiology*; D013997:Time Factors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D017470:Receptors, Glutamate; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D001418:Baclofen; D004298:Dopamine