Role of kappa-opioid receptors in the effects of salvinorin A and ketamine on attention behavior in rats

Title:
Role of kappa-opioid receptors in the effects of salvinorin A and ketamine on attention behavior in rats
Authors:
Nemeth, Christina L.; Paine, Tracie A.; Rittiner, Joseph E.; Béguin, Cécile; Carroll, F. Ivy; Roth, Bryan L.; Cohen, Bruce M.; Carlezon, William A., Jr.
Abstract:
Background: Disruptions in perception and cognition are characteristic of psychiatric conditions such as schizophrenia. Studies of pharmacological agents that alter perception and cognition in humans might provide a better understanding of the brain substrates of these complex processes. One way to study these states in rodents is with tests that require attention and visual perception for correct performance. Methods: We examined the effects of two drugs that cause disruptions in perception and cognition in humans—the kappa-opioid receptor (KOR) agonist salvinorin A (salvA; 0.125–4.0 mg/kg) and the non-competitive NMDA receptor antagonist ketamine (0.63–20 mg/kg)—on behavior in rats using the 5-choice serial reaction time task (5CSRTT), a food-motivated test that quantifies attention. We also compared the binding profiles of salvA and ketamine at KORs and NMDA receptors. Results: SalvA and ketamine produced the same pattern of disruptive effects in the 5CSRTT, characterized by increases in signs often associated with reduced motivation (omission errors) and deficits in processing (elevated latencies to respond correctly). Sessions in which rats were fed before testing suggest that reduced motivation produces a subtly different pattern of behavior. Pretreatment with the KOR antagonist JDTic (10 mg/kg) blocked all salvA effects and some ketamine effects. Binding and function studies revealed that ketamine is a full agonist at KORs, although not as potent or selective as salvA. Conclusions: SalvA and ketamine have previously under-appreciated similarities in their behavioral effects and pharmacological profiles. By implication, KORs might be involved in some of the cognitive abnormalities observed in psychiatric disorders such as schizophrenia.
Citation:
Nemeth, C., T. A. Paine, J. Rittiner, C. Beguin, F. I. Carroll, B. L. Roth, B. M. Cohen, and W. A. Carlezon, Jr. 2010. "Role of kappa-opioid receptors in the effects of salvinorin A and ketamine on attention behavior in rats." Psychopharmacology 210: 263-274.
Publisher:
Springer Verlag
DATE ISSUED:
2010
Department:
Neuroscience
Type:
article
PUBLISHED VERSION:
10.1007/s00213-010-1834-7
PERMANENT LINK:
http://hdl.handle.net/11282/309127

Full metadata record

DC FieldValue Language
dc.contributor.authorNemeth, Christina L.en_US
dc.contributor.authorPaine, Tracie A.en_US
dc.contributor.authorRittiner, Joseph E.en_US
dc.contributor.authorBéguin, Cécileen_US
dc.contributor.authorCarroll, F. Ivyen_US
dc.contributor.authorRoth, Bryan L.en_US
dc.contributor.authorCohen, Bruce M.en_US
dc.contributor.authorCarlezon, William A., Jr.en_US
dc.date.accessioned2013-12-23T16:03:00Zen
dc.date.available2013-12-23T16:03:00Zen
dc.date.issued2010en
dc.identifier.citationNemeth, C., T. A. Paine, J. Rittiner, C. Beguin, F. I. Carroll, B. L. Roth, B. M. Cohen, and W. A. Carlezon, Jr. 2010. "Role of kappa-opioid receptors in the effects of salvinorin A and ketamine on attention behavior in rats." Psychopharmacology 210: 263-274.en_US
dc.identifier.issn0033-3158en_US
dc.identifier.urihttp://hdl.handle.net/11282/309127en
dc.description.abstractBackground: Disruptions in perception and cognition are characteristic of psychiatric conditions such as schizophrenia. Studies of pharmacological agents that alter perception and cognition in humans might provide a better understanding of the brain substrates of these complex processes. One way to study these states in rodents is with tests that require attention and visual perception for correct performance. Methods: We examined the effects of two drugs that cause disruptions in perception and cognition in humans—the kappa-opioid receptor (KOR) agonist salvinorin A (salvA; 0.125–4.0 mg/kg) and the non-competitive NMDA receptor antagonist ketamine (0.63–20 mg/kg)—on behavior in rats using the 5-choice serial reaction time task (5CSRTT), a food-motivated test that quantifies attention. We also compared the binding profiles of salvA and ketamine at KORs and NMDA receptors. Results: SalvA and ketamine produced the same pattern of disruptive effects in the 5CSRTT, characterized by increases in signs often associated with reduced motivation (omission errors) and deficits in processing (elevated latencies to respond correctly). Sessions in which rats were fed before testing suggest that reduced motivation produces a subtly different pattern of behavior. Pretreatment with the KOR antagonist JDTic (10 mg/kg) blocked all salvA effects and some ketamine effects. Binding and function studies revealed that ketamine is a full agonist at KORs, although not as potent or selective as salvA. Conclusions: SalvA and ketamine have previously under-appreciated similarities in their behavioral effects and pharmacological profiles. By implication, KORs might be involved in some of the cognitive abnormalities observed in psychiatric disorders such as schizophrenia.en_US
dc.publisherSpringer Verlagen_US
dc.identifier.doi10.1007/s00213-010-1834-7en
dc.subject.departmentNeuroscienceen_US
dc.titleRole of kappa-opioid receptors in the effects of salvinorin A and ketamine on attention behavior in ratsen_US
dc.typearticleen_US
dc.identifier.journalPsychopharmacologyen_US
dc.identifier.volume210en_US
dc.identifier.startpage263en_US
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