Table 3.
Small-molecule manipulations of the CRF system in nicotine use.
| Target | Drug/compound | Result | Reference |
|---|---|---|---|
| CRF | Viral overexpression (AAV2/5-CRF) | Increase in CRF2/CRF1 gene expression ratio and decrease in dysphoric-like behavior during nicotine withdrawal (bilateral intra-VNST) | (Qi et al., 2016) |
| Increase in nicotine self-administration and CRF1/CRF2 gene expression in females compared with males (bilateral intra-NAc) | (Uribe et al., 2019) | ||
| CRF1 receptor | Antagonist (R278995/CRA-0450) | Prevention of elevation of brain reward thresholds during withdrawal- and stress-induced reinstatement of nicotine seeking (i.c.v.) | (Bruijnzeel et al., 2009) |
| Prevention of elevation of brain reward thresholds during withdrawal (bilateral intra-CeA) | (Bruijnzeel, 2012a) | ||
| CRF1 receptor | Antagonist (R121919) | Decrease in thermal hyperalgesia during nicotine withdrawal and reinstatement of nicotine seeking (s.c.) | (Baiamonte et al., 2014) |
| CRF1 receptor | Antagonist (MPZP) | Prevention of nociceptive hypersensitivity and increase in nicotine intake following abstinence (bilateral intra-CeA) | (Cohen et al., 2015) |
| Prevention of aversive effects of nicotine withdrawal and limited escalation of intake (bilateral intra-VTA) | (Grieder et al., 2014) | ||
| Blockade of anxiety-like behavior during withdrawal and decrease in nicotine self-administration (s.c.) | (George et al., 2007) | ||
| CRF1 receptor | Antagonist (antalarmin) | Alleviation of anxiety-like behavior and decrease in neuronal activation (intra-IPN) | (Zhao-Shea et al., 2015) |
| CRF1/CRF2 receptor | Antagonist (D-Phe CRF12–41) | Decrease in stress-induced reinstatement of nicotine seeking (i.c.v.) | (Zislis et al., 2007) |
| Prevention of elevation of brain reward thresholds during nicotine withdrawal (i.c.v.) | (Bruijnzeel et al., 2007) | ||
| Prevention of withdrawal-induced elevation of brain reward thresholds (intra-NAc and intra-CeA but not intra-BNST) | (Marcinkiewcz et al., 2009) | ||
| CRF2 receptor | Agonist (Ucn2, Ucn3) | Decrease in anxiety-like behavior following acute nicotine withdrawal (i.c.v.) | (Bagosi et al., 2016) |
| CRF2 receptor | Antagonist (astressin-2B) | No prevention of elevation of brain reward thresholds or stress-induced reinstatement of nicotine seeking (i.c.v.) | (Bruijnzeel et al., 2009) |
| CRF-BP | Antagonist (CRF[6–33]) | Blunting of weight gain during nicotine withdrawal (i.c.v.) | (Heinrichs et al., 1996) |
BP, binding protein; BNST, bed nucleus of the stria terminalis; NAc, nucleus accumbens; IPN, interpeduncular nucleus.