Cognitive impairment and persistent changes in exploration and hyperactivity in mice after withdrawn from chronic cocaine

Abstract

Lasting neurobehavioral adaptations such as cognitive decline are induced by chronic cocaine exposure in animal models. However, persistent changes in motor and exploratory responses are rarely reported. In this study, mice were administered a cocaine dose (COC, 20 mg/kg/day) or saline (SAL) repeatedly for 12 consecutive days in their home cage. After 24 days of drug withdrawal, they were submitted to a behavioral test battery to assess motor/exploratory activity and anxiety-like behavior (elevated plus maze and open field tests), behavioral despair (forced swimming test), working and reference memory (spontaneous alternation behavior –SAB- and novel place recognition memory tests). This behavioral assessment was carried out in drug-free conditions and in unfamiliar environments, so no cocaine-associated stimuli were presented. The cocaine-withdrawn mice showed cognitive deficits in spontaneous alternation behavior and place recognition memory. Importantly, they also displayed hyperlocomotion, increased rearing activity and altered exploratory patterns in different tasks. In the forced swimming test, they were more active (struggled/climbed more) when trying to escape from the water albeit showing similar immobility behavior than controls. In conclusion, in addition to cognitive deficits, chronic cocaine may induce lasting changes in psychomotor activation even in unfamiliar environments not associated to the drug. This outcome may be influenced by factors related to exploration, energy or emotionality.