DISTINCT TEMPORAL WINDOWS OF SLEEP REGULATE THE FORMATION OF COCAINE CONDITIONED PLACE PREFERENCE

Conditioned place preference (CPP) is a widely used model to study drug-associated contextual memory, yet the role of sleep as a post-acquisition window for cocaine-seeking behavior remains unclear. We tested whether sleep deprivation (SD) applied at distinct post-conditioning intervals alters the CPP formation in rats. CPP was induced over 4 days (cocaine 15mg/kg, i.p., or saline), and preference was quantified using a preference index (PI). Animals underwent SD either 3h (early SD) or 5h (delayed SD) after CPP sessions. Prior to the behavioral experiments, we characterized the acute cocaine effects in a different set of animals. Cocaine induced transient hyperlocomotion accompanied by increased hippocampal theta and cortical gamma oscillations. Approximately 3h after administration, animals showed sleep rebound with increased mPFC delta (0.5–4Hz) power [+17.98%; F(2, 13)= 37,52, p< 0.001]. Behavioral analyses revealed increased place preference in the early SD group [F(3, 25), p= 0.0128; Tukey’s test SAL Sleep vs COCA Early SD, p= 0.0182)]. Both Cocaine sleep [PI=44.7%, p= 0.0239] and cocaine SD [PI=70%, p= 0.0197] showed enhanced preference versus saline sleep [PI=-3%, p= 0.7118]. Delayed SD nearly abolished CPP [PI=7%, p= 0.9661]. The observed delta sleep rebound likely reflects homeostatic renormalization of cocaine-induced activation networks. Blocking this early phase of sleep would prevent synaptic downscaling, thereby potentiating place preference. In contrast, abolition of place preference following delayed deprivation indicate memory stabilization mainly relies on a late, REM-rich window.