AMPA/kainate, NMDA, and dopamine D1 receptor function in the nucleus accumbens core: a context-limited role in the encoding and consolidation of instrumental memory.
Neural integration of glutamate- and dopamine-coded signals within the nucleus accumbens (NAc) is a fundamental process governing cellular plasticity underlying reward-related learning. Intra-NAc core blockade of NMDA or D1 receptors in rats impairs instrumental learning (lever-pressing for sugar pellets), but it is not known during which phase of learning (acquisition or consolidation) these receptors are recruited, nor is it known what role AMPA/kainate receptors have in these processes. Here we show that pre-trial intra-NAc core administration of the NMDA, AMPA/KA, and D1 receptor antagonists AP-5 (1 microg/0.5 microL), LY293558 (0.01 or 0.1 microg/0.5 microL), and SCH23390 (1 microg/0.5 microL), respectively, impaired acquisition of a lever-pressing response, whereas post-trial administration left memory consolidation unaffected. An analysis of the microstructure of behavior while rats were under the influence of these drugs revealed that glutamatergic and dopaminergic signals contribute differentially to critical aspects of the initial, randomly emitted behaviors that enable reinforcement learning. Thus, glutamate and dopamine receptors are activated in a time-limited fashion-only being required while the animals are actively engaged in the learning context.
Hernandez
Pepe J
PJ
Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisconsin 53719, USA. phernand@wisc.edu
Andrzejewski
Matthew E
ME
Sadeghian
Kenneth
K
Panksepp
Jules B
JB
Kelley
Ann E
AE
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001552:Benzazepines / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology*; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D008845:Microinjections; D009714:Nucleus Accumbens / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology
D001552:Benzazepines; D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D007546:Isoquinolines; D018091:Receptors, AMPA; D017447:Receptors, Dopamine D1; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D013777:Tetrazoles; C082309:tezampanel