title: Simultaneous AMPA/kainate receptor blockade and dopamine D(2/3) receptor stimulation in the nucleus accumbens decreases brain stimulation reward in rats.
abstract: Interactions between dopamine (DA) and glutamate (GLU) in the mesocorticolimbic pathway of the brain may influence motivation and reward. Previous work from this laboratory has demonstrated that alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptor blockade may potentiate decreases in exploratory motor activity induced by the DA D(2/3) receptor agonist 7-OH-DPAT in the nucleus accumbens septi (NAS). This study investigated the interaction of AMPA/kainate receptor antagonists CNQX or NBQX with 7-OH-DPAT on ventral tegmental area (VTA) brain stimulation reward (BSR). Effects of these compounds, alone and combined, were measured in male Sprague-Dawley rats stereotaxically implanted with a unilateral VTA electrode and bilateral guide cannulae in the NAS core or shell subregions. Rate-frequency analysis was used to assess BSR frequency thresholds and maximum response rates of rats trained to lever-press for reinforcing electrical stimulation. When given alone, CNQX (0.5 microg), NBQX (0.5 microg), or 7-OH-DPAT (5.0 microg) did not affect BSR frequency thresholds. Co-administration of CNQX or NBQX with 7-OH-DPAT synergistically increased BSR frequency thresholds, indicative of decreased reward. These data indicate that simultaneous AMPA/kainate receptor blockade and DA D(2/3) receptor stimulation in the NAS may act synergistically to inhibit motivated behaviours such as electrical brain self-stimulation.
authors.affiliation: Department of Psychiatry, NC6.524 University of Texas, Southwestern Medical Center, Dallas, TX 75390-9070, USA.
authors.forename: Kwang-Ho
authors.initials: KH
authors.lastname: Choi
authors.forename: Robert L H
authors.initials: RL
authors.lastname: Clements
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Greenshaw
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D065127:Dopamine D2 Receptor Antagonists; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D008297:Male; D008845:Microinjections / Q000379:methods; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors / Q000502:physiology*; D012044:Regression Analysis; D012201:Reward; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000502:physiology* / Q000528:radiation effects
chemical_list: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D065127:Dopamine D2 Receptor Antagonists; D011810:Quinoxalines; D018091:Receptors, AMPA; D017448:Receptors, Dopamine D2; D018092:Kainic Acid Receptors; D013764:Tetrahydronaphthalenes; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C031349:7-hydroxy-2-N,N-dipropylaminotetralin