Oscillatory power and synchrony in the rat forebrain are altered by a sensitizing regime of D-amphetamine

Repeated injections of psychostimulants, such as D-amphetamine (D-AMPH), provide a well-validated model of progressive cellular and systems-level alterations in brain function and behavior associated with addiction. The present study employed quantitative measures of both power spectral density and synchrony from local field potentials (LFPs) recorded simultaneously from the prefrontal cortex (PFC), parietal cortex (PAR), and hippocampus (HPC) in awake, behaving rats to assess changes in oscillations during different stages of D-AMPH-induced sensitization. The induction and development of sensitization altered the power of multiple frequency bands in a brain region-specific manner, whereas no changes were observed in animals treated with chronic saline. Specifically, the induction of sensitization to D-AMPH was accompanied by alterations in delta (2-5 Hz) and theta (5-11 Hz) oscillations similar to those observed in EEG recordings from addicted individuals describing craving and hedonic experience of the drug. Sensitization was also related to increased theta coherence between the PFC and HPC, along with suppression of cross-frequency correlations between theta and fast-gamma (65-100 Hz) in both the HPC and the PFC. Collectively, the present findings indicated the induction of a state in which the timing and synchronizing effects of oscillations are altered by sensitization to D-AMPH and are especially pronounced in the PFC. Furthermore, numerous LFP-derived measures were characterized that may serve as objective physiological correlates of pathological states observed in addiction.