Table 2.
Summary of Preclinical Studies of TBI and Drug Reward, Reinforcement, and Seeking
| TBI Model | Single/Repeated Injury | Drug of Abuse | Reward/Reinforcement Model | Species/Strain | Sex | Age at Time of Injury | TBI→Testing Delay | Effect of TBI | Reference |
|---|---|---|---|---|---|---|---|---|---|
| TBI→Drug | |||||||||
| CCI (closed head) | Single | Alcohol | Two-bottle choice (drinking in the dark) | Mouse/C57BL/6 | M | 6–7 wk | 4–10 days | Reduced intake | (37) |
| Weight drop | Single | Alcohol | Two-bottle choice | Mouse/Swiss Webster (selectively bred for stress analgesia) | NS | 8 wk | 7–19 days | Reduced intake (only in LA mice) | (36) |
| 62–72 days | No effect | ||||||||
| Blast | Single | Alcohol | Two-bottle choice Two-bottle choice (alcohol deprivation and quinine adulteration tests) |
Rat/Sprague Dawley | M | 8 wk | 1–7 wk | No effect | (38) |
| 8 wk | Increased 1-hour intake in upper 50% after median split | ||||||||
| 10–24 wk | No effect | ||||||||
| CCI (closed head) | Single | Alcohol | Two-bottle choice | Mouse/Swiss Webster | M | 21 days | 10–22 days | Increased intake | (40) |
| CCI (closed head) | Single | Alcohol | Two-bottle choice | Mouse/Swiss Webster | M | 21 days | 8–9 wk | No effect | (41) |
| F | 21 days | 8–9 wk | Increased intake | ||||||
| M | 60 days | 3–4 wk | No effect | ||||||
| F | 60 days | 3–4 wk | No effect | ||||||
| CCI (closed head) | Single | Alcohol | CPP | Mouse/Swiss Webster | M | 21 days | 8–9 wk | No effect | (41) |
| F | 21 days | 8–9 wk | Increased CPP | ||||||
| Blast | Single Repeated (3×) | Alcohol | Two-bottle choice | Mouse/C57BL/6 | M | 12–16 wk | 4–8 wk | No effect Decreased 24-hour intake Increased 2-hour proportional intake |
(39) |
| CCI (open head) | Single | Cocaine | CPP | Mouse/C57BL/6 | M | 6 wk | 2–3 wk | Increased CPP | (42,43) |
| CCI (open head) | Single | Cocaine | CPP | Mouse/C57BL/6 | M | 6 wk | 2–3 wk | Increased CPP | (44) |
| 8 wk | 2–3 wk | No effect | |||||||
| CCI (open head) | Single | Cocaine | CPP | Mouse/C57BL/6 | F (E/P)a F (M/D)b |
6 wk | 2–3 wk | No effect Increased CPP |
(44) |
| CCI (open head) | Single | Cocaine | SA | Rat/Long-Evans | M | 12 wk | 2–4 wk | Increased SA | (46) |
| Blast | Single | Cocaine | SA | Rat/Sprague Dawley | M | 8 wk | 4–8 wk | No effect on SA | (47) |
| 10–11 wk | No effect on extinction | ||||||||
| 12–14 wk | No effect on cue- or drug-primed reinstatement | ||||||||
| Blast | Repeated (3×) | Oxycodone | SA | Rat/Sprague Dawley | M | 8 wk | 4–8 wk | No effect on FR-1 SA | (48) |
| 5–7 wk | Reduced FR-2 SA; no effect on FR-4 SA | ||||||||
| 7–9 wk | Increased drug seeking in FR-4 extinction sessions | ||||||||
| 10–23 wk | No effect on FR-1 extinction or cue reinstatement of drug seeking | ||||||||
| Blast | Repeated (3×) | Oxycodone | SA | Rat/Sprague Dawley | M | 8 wk | 6 wk | Increased drug seeking | (123) |
| Drug→TBI→Drug | |||||||||
| LFP | Single | Alcohol | Operant alcohol SA | Rat/Wistar | F | 16 wk | 2–10 days | No effect | (128) |
| LFP | Single | Alcohol | Operant alcohol SA | Rat/Wistar | M | 16 wk | 9 days | Increased breakpoint for alcohol | (129) |
| LFP | Single | Alcohol | Operant alcohol SA | Rat/Wistar | M | 16 wk | 2–15 days | Increased alcohol SA: preinjury intake positively correlated with postinjury increase in intake | (130) |
CCI, controlled cortical impact; CPP, conditioned place preference; F, female; FR, fixed ratio; LA, low analgesia; LFP, lateral fluid percussion; M, male; NS, not specified; SA, self-administration; TBI, traumatic brain injury.
a
Phase at time of injury; E/P, estrus/proestrus.
b
Phase at time of injury; M/P, metestrus/diestrus.