Table 9.
Neurotrophins and miscellaneous targets in fear extinction (preclinical studies).
| Neurotrophins | |||||
|---|---|---|---|---|---|
| Drug/manipulation | Extinction learning |
Extinction retrieval |
Long-term extinction |
Route | Reference |
| FGF2 | (+)# | + | ns | sc | (Graham & Richardson, 2009) |
| ns | +1 | + (Re-in) (Ren-A) | sc | (Graham & Richardson, 2009, 2010) | |
| ns | +1 | + (Ren-A) | BLA | (Graham & Richardson, 2011b) | |
| BDNF | No training | +**2 | No effect (Re-in) | IL | (Peters et al., 2010); (Rosas-Vidal et al., 2014) |
| No training | No effect2 | ns | PL | (Rosas-Vidal et al., 2014) | |
| 7.8-Dihydroxyflavone | (+)* | No effect | (+) (Re-in) | ip | (Andero et al., 2011) |
| No effect | No effect* | + (Ren-A) | ip | (Baker-Andresen et al., 2013) | |
| Lentiviral transfected dominant negative form of TrkB | No effect | − | ns | BLA | (Chhatwal et al., 2006) |
| BDNF KD in HPC | − | ns | ns | No drug | (Heldt et al., 2007) |
| Val66Met BDNF SNP | − | ns | ns | No drug | (Soliman et al., 2010) |
| BDNF +/− KO | −*** | −*** | ns | No drug | (Psotta et al., 2013) |
| BDNF antibody | − | − | ns | IL | (Rosas-Vidal et al., 2014) |
| No effect | No effect | ns | PL | (Rosas-Vidal et al., 2014) | |
| BDNF KO in forebrain | ns | No effect# | ns | PL | (Choi et al., 2010) |
| Methylene blue, nitric oxide, histamine, and LTCCs | |||||
| Methylene blue | ns | +1 | ns | ip | (Gonzalez-Lima & Bruchey, 2004) |
| ns | ns | +1* (Ren-A) | ip | (Wrubel et al., 2007) | |
| Histamine | ns | +1 | ns | CA1 | (Bonini et al., 2011) |
| Dimaprit (H2 ag) | ns | +1 | ns | CA1 | (Bonini et al., 2011) |
| Ranitidine (H2 ant) | ns | −1 | ns | CA1 | (Fiorenza et al., 2012) |
| ns | −1 | ns | BLA | (Fiorenza et al., 2012) | |
| ns | −1 | ns | PFC | (Fiorenza et al., 2012) | |
| SKF9188 (histamine methyl-transferase inhibitor) | ns | +1 | ns | CA1 | (Fiorenza et al., 2012) |
| ns | +1 | ns | BLA | (Fiorenza et al., 2012) | |
| ns | +1 | ns | PFC | (Fiorenza et al., 2012) | |
| L-NAME (nNOS inhibitor)4 | − | − | ns | ip | (Luo et al., 2014) |
| CamKII-Cre Cav1.2 KO | No effect | ns | ns | No drug | (McKinney et al., 2008) |
| Cav1.3 KO | No effect | ns | ns | No drug | (Busquet et al., 2008) |
| No effect | ns | ns | No drug | (McKinney & Murphy, 2006) | |
| Nifedipine (LTCC ant) | − | ns | ns | ip | (Cain et al., 2002) |
| No effect | ns | ns | icv | (Busquet et al., 2008) | |
| No effect | − | ns | BLA | (Davis & Bauer, 2012) | |
| ns | −1 | ns | HPC | (de Carvalho Myskiw et al., 2014) | |
| Verapamil (VGCC ant) | No effect | − | ns | BLA | (Davis & Bauer, 2012) |
Drug administration following extinction training;
drug administration 24 h prior extinction retrieval
drug administration 30 min prior extinction retrieva
ABA scheme, 40 mg/kg.
Facilitates rescue of impaired fear extinction;
facilitates extinction of remote memories,
only in older animals (7 months), younger ones (2 months) are not affected,
reduced fear expression at the beginning of extinction training.
+, improved; -, impaired; (+) or (−), only minor effects; ip, intraperitoneal injection; sc, subcutanous injection; icv, intracerebroventricular injection; ns, not studied; HPC, intra-hippocampal administration; BLA, intra-basolateral amygdala administration; IL, infralimbic cortex; PL, prelimbic cortex; CA1, cornu ammonis 1; Ren-A, Fear renewal in conditioning context; SR, spontaneous recovery; Re-in, reinstatement; ag, agonist; ant, antagonist, KO, knock-out;