Effects of methamphetamine-induced sleep disruption on intradimensional/extradimensional attentional set-shifting in adult rhesus monkeys.

Abstract

Cognitive performance has been shown to be negatively affected by both methamphetamine use and sleep disruption, independently. However, few studies have investigated the effects of methamphetamine-induced sleep disruptions on next-day executive functioning. The aim of the present study was to investigate the next-day cognitive effects of methamphetamine-induced sleep disruption on executive functioning in adult rhesus monkeys. Monkeys (4 males and 1 female) were fitted with primate collars to which actigraphy monitors were attached. Actigraphy-based sleep measures were assessed at night during baseline conditions and after methamphetamine administration (0.3 and 0.56 mg/kg, i.m.) 3 hours before "lights off." The monkeys then completed an intradimensional/extradimensional attentional set-shifting task (Cambridge Neuropsychological Test Automated Battery touchscreen system) the following day. Methamphetamine administration disrupted actigraphy-based sleep parameters, significantly decreasing sleep efficiency and increasing % wake, sleep latency, and sleep fragmentation at the highest dose tested (0.56 mg/kg) compared with baseline. Sleep impairment was associated with next-day cognitive deficits after treatment with methamphetamine at the dose of 0.56 mg/kg, with significantly increased total trials to completion, total errors, and total perseverative errors and decreased mean task accuracy compared with cognitive performance during baseline. Significant correlations were observed between actigraphy-based sleep measures and cognitive performance across all experimental conditions, with greater wake time and lower sleep efficiency being associated with worse cognitive performance. Our findings indicate that the sleep-disrupting effects of methamphetamine may play a role in this drug's cognition-disrupting effects. SIGNIFICANCE STATEMENT: The present study shows that methamphetamine-induced sleep disruption is associated with next-day impairments in cognitive measures in nonhuman primates. Addressing sleep disruptions may offer a novel treatment strategy to improving cognitive deficits associated with use of this stimulant.