Phosphodiesterase Inhibitor ‘Rolipram’ Alleviates Sleep-Deprivation-Mediated Appetitive-Delay-Conditioned Memory in the Rat

Sleep deprivation (SD) disrupts memory consolidation, including amygdala-dependent processes such as appetitive delay-conditioned memory. SD impairs this form of conditioning by inducing deficits in the formation of associations between conditioned and unconditioned stimuli, likely by reducing cAMP signaling in the amygdala. Rolipram, a phosphodiesterase-4 inhibitor, prevents cAMP breakdown, enhancing PKA and CREB activity, which are vital for long-term memory formation. The reversibility of SD-mediated learning impairment through pharmacological means remains unclear. We hypothesized that rolipram microinjection into the central nucleus of the amygdala (CeA) could alleviate SD-induced memory impairments. Rats were surgically prepared for drug microinjection and sleep–wake recording. The conditioned stimulus, a house light, and the unconditioned stimulus, mango juice, were used to train the animals on an appetitive delay-conditioning task. Mango juice was delivered through a juice dispensing window, and the number of head entries into the window to obtain juice was considered a learning outcome. Rolipram or vehicle was microinjected into the CeA in two independent groups shortly after training, followed by 6 h of SD. The non-SD and SD-Rolipram groups made significantly more head entries than the SD-Vehicle groups. Nevertheless, the SD-Vehicle animals exhibited less number of head entries. These findings indicate that Rolipram mitigated the SD-induced impairment of appetitive delay-conditioned memory, suggesting that it may have therapeutic potential for treating cognitive deficits in conditions like Alzheimer’s disease and other forms of dementia. Investigating the long-term impact of sleep deprivation on dementia in humans and the therapeutic potential of phosphodiesterase inhibitors as drugs may provide valuable insights.