Simultaneous AMPA/kainate receptor blockade and dopamine D(2/3) receptor stimulation in the nucleus accumbens decreases brain stimulation reward in rats.
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.
Choi
Kwang-Ho
KH
Department of Psychiatry, NC6.524 University of Texas, Southwestern Medical Center, Dallas, TX 75390-9070, USA.
Clements
Robert L H
RL
Greenshaw
Andrew J
AJ
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
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