Sleep deprivation impairs the extinction of cocaine-induced environmental conditioning in mice.

Persistence of a drug-environment conditioning induced by repeated psychostimulant treatment is thought to play a key role in the addictive cycle. In addition, sleep disorders are a common feature in patients with addictive disorders. Sleep deprivation shares similar neurobiological effects with psychostimulants. Therefore, we investigated whether sleep deprivation would impair the extinction of previously established conditioning between the drug effect and the environmental cues. Four cohorts of male adult mice underwent a behavioral sensitization procedure pairing drug (cocaine at 15 mg/kg, i.p.) or saline with environment (open-field apparatus). The extinction of conditioned locomotion was evaluated after control (home-cage maintained) or sleep deprivation (gentle handling method for 6h) conditions. Sleep deprivation both postponed the initiation and impaired the completeness of extinction of the conditioned locomotion promoted by previous drug-environment conditioning in cocaine-sensitized animals. While the cocaine control group required 5 free-drug sessions of exposure to the open-field apparatus to complete extinction of conditioned locomotion, the cocaine pre-treated group that experienced sleep deprivation before each extinction session still significantly differed from its respective control group on Day 5 of extinction. The possibility that the sleep condition can influence the extinction of a long-lasting association between drug effects and environmental cues can represent new outcomes for clinically relevant phenomena.

Food restriction increases long-term memory persistence in adult or aged mice.

Food restriction (FR) seems to be the unique experimental manipulation that leads to a remarkable increase in lifespan in rodents. Evidences have suggested that FR can enhance memory in distinct animal models mainly during aging. However, only few studies systemically evaluated the effects FR on memory formation in both adult (3-month-old) and aged (18-24-month-old) mice. Thus, the aim of the present study was to investigate the effects of acute (12h) or repeated (12h/day for 2days) FR protocols on learning and memory of adult and aged mice evaluated in the plus-maze discriminative avoidance task (PM-DAT), an animal model that concurrently (but independently) evaluates learning and memory, anxiety and locomotion. We also investigated the possible role of FR-induced stress by the corticosterone concentration in adult mice. Male mice were kept at home cage with food ad libitum (CTRL-control condition) or subjected to FR during the dark phase of the cycle for 12h/day or 12h/2days. The FR protocols were applied before training, immediately after it or before testing. Our results demonstrated that only FR for 2days enhanced memory persistence when applied before training in adults and before testing in aged mice. Conversely, FR for 2days impaired consolidation and exerted no effects on retrieval irrespective of age. These effects do not seem to be related to corticosterone concentration. Collectively, these results indicate that FR for 2days can promote promnestic effects not only in aged mice but also in adults.