Table II.
Predicted therapeutic role of corticotropin-releasing factor (CRF) receptor antagonists in modulating processes related to drug addiction
| Drug | Acute HPA activation |
Behavioural sensitization |
Self-administration |
Withdrawal- induced place aversion |
Anxiety during withdrawal/ abstinence |
Relapse |
||
|---|---|---|---|---|---|---|---|---|
| maintenance | dependent/escalated drug taking |
stress-induced reinstatement |
drug- or cue-induced reinstatement |
|||||
| Cocaine | ↓ [51]a | ↓ [54]b | –/↓ [94-96]b,c | ↓ [94]b | ↓ [97]a | ↓ [98,99]b | –/↓ [98]a; [54,100]b | |
| Opiates | ↓ [101]b | _[102]b | ↓ [102,103]b | ↓ [104,105]b | ↓ [106]a; [99,107]b | –/↓ [106]a; [107]b | ||
| Ethanol | ↓ [108]a | ↓ [53,55]b | –/↓ [76,91,92,109-115]b,c | ↓ [116]a, [73,91,92,109,114-116]b |
↓ [116,117]a; [91,92,118]b |
↓ [119]a; [91,110,120]b,c |
–/↓ [119]a; [121]b | |
| Nicotine | ↓ [122]b | ↓ [123]a | _[64]b | ↓ [64]b | ↓ [124]a[64]b | ↓ [125,126]b | ||
| Δ9-tetrahydro- cannabinol |
↓ d | ↓ [127]a | ↓ e | |||||
| Palatable food | ↓ [128]b | ↓ [128]b | ↓ [129]b | _[129]b | ||||
Studies used CRF receptor subtype nonspecific antagonists.
Studies used CRF receptor-specific antagonists.
Systemic CRF receptor antagonism not yet tested with cannabinoid agonist exposure, but decreases in HPA activation and sensitization are predicted based on the ability of CRF receptor antagonists to inhibit similar effects following exposure to other drugs of abuse in conjunction with activation of the HPA axis by the cannabinoid receptor agonist anandamide[48] (although intracerebroventricular administration of D-Phe CRF12-41 does not significantly alter corticosterone levels after acute cannabinoid agonist administration).[127]
Systemic CRF receptor antagonism not yet tested with cannabinoid agonist exposure, but elevated anxiety-like behaviour and extracellular CRF observed in the extended amygdala during withdrawal from chronic cannabinoid agonist treatment.[69]
HPA = hypothalamic-pituitary-adrenal; ↓ indicates attenuation of HPA activation or behavioural measure following CRF receptor antagonist treatment; – indicates no effect of CRF receptor antagonist treatment on given behaviour.