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Effects of traumatic brain injury on oxycodone self‐administration in rats

Epidemiological data indicate that patients who experience a traumatic brain injury (TBI) have an elevated risk of developing substance abuse disorders, but the underlying neurobiological connections remain unclear. To further understand the relationship between TBI and substance abuse, we investigated the effects of TBI on the rewarding effects of oxycodone in clinically‐relevant models. Our evaluation utilized lateral fluid percussion injury of moderate severity followed by assessment of oxycodone self‐administration behavior in adult male Sprague‐Dawley rats. The reinforcing effects of oxycodone were examined under fixed ratio (FR) and progressive ratio (PR) schedules as well as in a reinstatement model of relapse. Relative to control, TBI subjects self‐administered greater levels of the intermediate doses of oxycodone under FR conditions and exhibited up to 8‐fold higher responding during time out periods when no drug or cues were available. Under PR conditions, multiple doses of oxycodone also maintained higher break points in TBI subjects when compared to sham controls. Conversely, no differences based on injury condition were observed following cue‐ and prime‐induced reinstatement of behavior following extinction of oxycodone self‐administration. Consistent with previous acquisition data, significant differences were noted in oxycodone's reinforcing effects following TBI which suggest an enhanced reinforcing potential in injured subjects. The perseverative responding noted during time out periods may reflect elevated impulsivity levels or compulsive drug seeking behavior. Research supported by DoD grant W81XWH‐11‐1‐0374.