Cognitive effects of psychotomimetic drugs in rats discriminating number cues.
BACKGROUND
Deficits in memory and attention are broadly acknowledged during psychosis; however, experiments on modeled psychosis often test working memory without systematic manipulation of attentional demands.


OBJECTIVE
The major research goal was discovering which neurobehavioral processes, attention, or memory contributed more to drug-provoked performance deficits.


METHODS
Rats were trained to perform operant ratio discrimination (RD) tasks wherein the number of presses at a rear-wall lever was discriminated using one of two front-wall levers. Effects from four psychotomimetic drugs, the serotonin agonist 2,5-dimethoxy-4-iodoamphetamine, the noncompetitive NMDA-glutamate receptor antagonist phencyclidine (PCP), and two CB1-selective cannabinoid agonists, WIN 55,512-2 and AM 411, were assessed using a signal detection analytical overlay to dissociate cognitive from noncognitive motor and motivational disruptions. Further methods allowed dissociation of attention compromises from mnemonic deficits.


RESULTS
For each test compound, at least one dose elicited decreased RD accuracy without affecting response rates, and task difficulty was shown to be a crucial dictator of accuracy effect specificities. Effects from both PCP and WIN 55,512-2 biased animals to select the response lever conditioned for denser reinforcement. The same two drugs rendered peculiar response patterns in distracter light session components, considering light blinks were included to divert subjects' attention away from task-relevant information. The response patterns determined during distracter components of PCP/WIN testing sessions, counterintuitively, suggest performance enhancement.


CONCLUSIONS
Comprehensive viewing of RD performance patterns after drug administration indicates that sustained attention and transient information management are significantly impaired during the drug-induced psychosis state, while selective attention is less affected.
Raabe College of Pharmacy, Ohio Northern University, Ada, OH 45810, USA. cwillmor@harding.edu
C B
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Willmore
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Krall
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Spears
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Makriyannis
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Elmer
D000218:Adamantane / Q000031:analogs & derivatives / Q000633:toxicity; D000662:Amphetamines / Q000633:toxicity; D000818:Animals; D001288:Attention / Q000187:drug effects*; D003071:Cognition / Q000187:drug effects*; D004193:Discrimination Learning / Q000187:drug effects*; D013759:Dronabinol / Q000031:analogs & derivatives / Q000633:toxicity; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity; D008297:Male; D010622:Phencyclidine / Q000633:toxicity; D051381:Rats; D020318:Rats, Long-Evans; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012054:Reinforcement, Psychology; D017366:Serotonin Receptor Agonists / Q000633:toxicity
C496392:(-)-adamantyl-delta8-tetrahydrocannabinol; D000662:Amphetamines; D018691:Excitatory Amino Acid Antagonists; D043884:Receptor, Cannabinoid, CB1; D016194:Receptors, N-Methyl-D-Aspartate; D017366:Serotonin Receptor Agonists; D013759:Dronabinol; D010622:Phencyclidine; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D000218:Adamantane