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.
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 andketamine at KORs and NMDA receptors. RESULTS:SalvA andketamine 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 andketamine 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.
Authors: John H Krystal; D Cyril D'Souza; Daniel Mathalon; Edward Perry; Aysenil Belger; Ralph Hoffman Journal: Psychopharmacology (Berl) Date: 2003-09-02 Impact factor: 4.530
Authors: Feng Yan; Ruslan V Bikbulatov; Viorel Mocanu; Nedyalka Dicheva; Carol E Parker; William C Wetsel; Philip D Mosier; Richard B Westkaemper; John A Allen; Jordan K Zjawiony; Bryan L Roth Journal: Biochemistry Date: 2009-07-28 Impact factor: 3.162
Authors: Hilarie C Tomasiewicz; Mark S Todtenkopf; Elena H Chartoff; Bruce M Cohen; William A Carlezon Journal: Biol Psychiatry Date: 2008-07-17 Impact factor: 13.382
Authors: Sungho Maeng; Carlos A Zarate; Jing Du; Robert J Schloesser; Joseph McCammon; Guang Chen; Husseini K Manji Journal: Biol Psychiatry Date: 2007-07-23 Impact factor: 13.382
Authors: Gabriella Aviello; Francesca Borrelli; Francesca Guida; Barbara Romano; Kevin Lewellyn; Maria De Chiaro; Livio Luongo; Jordan K Zjawiony; Sabatino Maione; Angelo A Izzo; Raffaele Capasso Journal: J Mol Med (Berl) Date: 2011-04-16 Impact factor: 4.599
Authors: Panos Zanos; Ruin Moaddel; Patrick J Morris; Lace M Riggs; Jaclyn N Highland; Polymnia Georgiou; Edna F R Pereira; Edson X Albuquerque; Craig J Thomas; Carlos A Zarate; Todd D Gould Journal: Pharmacol Rev Date: 2018-07 Impact factor: 25.468
Authors: Rachel J Donahue; Archana Venkataraman; F Ivy Carroll; Edward G Meloni; William A Carlezon Journal: Biol Psychiatry Date: 2015-06-19 Impact factor: 13.382