Cognitive effects of psychotomimetic drugs in rats discriminating number cues.

Deficits in memory and attention are known in psychosis, but experiments often test working memory without systematically varying attentional demands. This study used rats trained on operant ratio discrimination tasks to determine whether attention or memory contributes more to drug-induced performance deficits. Four psychotomimetic drugs—a serotonin agonist, the NMDA antagonist PCP, and two cannabinoid agonists—were assessed. A signal detection analysis dissociated cognitive from noncognitive disruptions. At least one dose of each drug decreased accuracy without affecting response rates, and task difficulty determined the specificity of accuracy effects. PCP and one cannabinoid biased animals toward the lever associated with denser reinforcement and produced peculiar response patterns during distracter light sessions, suggesting performance enhancement. Overall, sustained attention and transient information management were significantly impaired, while selective attention was less affected.

Study at a glance

Abstract

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