AMPA receptor antagonists reverse effects of extended habit training on signaled food approach responding in rats.
BACKGROUND
Dopamine D1 receptor stimulation is critically involved in early appetitive phases of learning in various behavioral paradigms. However, extended habit training was previously shown to reduce the ability of dopamine D1 receptor antagonists such as R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH-23390) to disrupt behavioral performance.


OBJECTIVE
The present study aimed to evaluate whether coadministration of glutamate alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) receptor antagonists restores sensitivity to acute blockade of D1 receptors.


METHODS
Adult male Wistar rats were presented with 45-mg food pellets delivered to the food tray, which was immediately preceded by a 400-ms tone (2.8 kHz, 78 dB). During each training and test session, there were 28 food-tone presentations with an average intertrial interval of 70 s, and each head entry into the food tray was recorded. Drug tests were conducted on either day 3 or 9 of the training using independent groups of animals. The main dependent variable was the number of trials during which no head-entry response was made during the 10-s period immediately after the food delivery.


RESULTS
Longer training duration enhanced the resistance of the signaled food approach behavior to extinction and to disrupting effects of supplementary food ration. Similarly, acute administration of SCH-23390 (0.04-0.16 mg/kg) dose-dependently reduced the number of omitted trials when given before the test session on day 3 but much less so when injected on day 9. AMPA receptor antagonists, NBQX (10 mg/kg) or GYKI-52466 (3-10 mg/kg), had no effects on their own but significantly enhanced the disrupting effects of SCH-23390 (0.08 and 0.16 mg/kg) when given on day 9 but not on day 3 of the training.


CONCLUSIONS
These results indicate that AMPA receptor blockade restores sensitivity to appetitive behavior-disrupting effects of SCH-23390 in subjects exposed to extended training protocol.
Bespalov
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Neuroscience Research, GPRD, Abbott, 67008, Ludwigshafen, Germany. anton.bespalov@abbott.com
Harich
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Jongen-Rêlo
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van Gaalen
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Gross
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D000818:Animals; D001070:Appetitive Behavior / Q000187:drug effects* / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology; D001569:Benzodiazepines / Q000008:administration & dosage / Q000494:pharmacology; D003214:Conditioning, Classical / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D005502:Food; D006184:Habits; D007274:Injections, Intraperitoneal; D011810:Quinoxalines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D013016:Sound; D013997:Time Factors
D001552:Benzazepines; D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D018091:Receptors, AMPA; D017447:Receptors, Dopamine D1; C061950:GYKI 52466; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D001569:Benzodiazepines