Table 5.
GABAergic signaling in fear extinction (preclinical studies).
| Facilitating GABA signaling | |||||
|---|---|---|---|---|---|
| Drug/manipulation | Extinction training | Extinction retrieval | Longterm extinction | Route | Reference |
| GABAA agonists GABA-binding site (αβ interface) | |||||
| Muscimol | +# | No effect | ns | BLA | (Akirav et al., 2006) |
| ns | +1,7 | ns | BLA | (Akirav et al., 2006) | |
| −# | − | ns | BLA | (Laurent et al., 2008), (Laurent & Westbrook, 2008) | |
| ns | −1 | ns | BLA | (Laurent & Westbrook, 2008) | |
| (+)# | − | ns | BLA | (Sierra-Mercado et al., 2011) | |
| − | − | ns | mPFC | (Laurent & Westbrook, 2008) | |
| ns | −1 | ns | mPFC | (Laurent & Westbrook, 2008) | |
| ns | No effect1 | ns | IL | (Akirav et al., 2006) | |
| +# | (+) | ns | IL | (Akirav et al., 2006) | |
| − | − | ns | IL | (Sierra-Mercado et al., 2011) | |
| No effect | − | ns | IL | (Laurent & Westbrook, 2009) | |
| (+)# | No effect | ns | PL | ((Laurent & Westbrook, 2009); (Sierra-Mercado et al., 2011)) | |
| ns | ns | + (Ren-A)8 | dHPC | (Corcoran et al., 2005) | |
| − | − | No effect (Ren-A) | dHPC | (Corcoran et al., 2005) | |
| (+)# | − | ns | vHPC | (Sierra-Mercado et al., 2011) | |
| GABAA: agonists BZD-binding site αγ interface) | |||||
| Chlordiazepoxide | − | ns | ns | ip | (Goldman, 1977) |
| ns | − | ns | ip | (Bouton et al., 1990) | |
| Diazepam | ns | − | ns | ip | (Pereira et al., 1989) |
| ns | − | ns | ip | (Bouton et al., 1990) | |
| Midazolam | ns | −1 | ns | ip | (Bustos et al., 2009) |
| −##6 | − | ns | ip | (Hart et al., 2009, 2010), (Hart et al., 2014) | |
| −#6 | − | ns | BLA | (Hart et al., 2009, 2010, 2014) | |
| GABAB receptor agonists | |||||
| Baclofen | ns | − | ns | ip | (Heaney et al., 2012) |
| GS39783 (positive modulator GABAB) | ns | No effect | ns | po | (Sweeney et al., 2013) |
| Inhibiting GABA signaling | |||||
| Drug/manipulation | Extinction learning | Extinction retrieval | Longterm extinction | Route | Reference |
| GAD67 KD in BLA | − | ns | ns | No drug | (Heldt et al., 2012) |
| GAD65 KO | −2 | −2 | ns | No drug | (Sangha et al., 2009) |
| α5 KD in HPC | ns | −3 | ns | No drug | (Yee et al., 2004) |
| α1 KO in CRF+ cells | − | − | ns | No drug | (Gafford et al., 2012) |
| Picrotoxin | ns | + | ns | ip | (McGaugh et al., 1990) |
| ns | +4 | ns | IL | (Thompson et al., 2010) | |
| ns | +4 | ns | PL | (Thompson et al., 2010) | |
| ns | +* | ns | (Fitzgerald et al., 2014b) | ||
| Bicuculline | ns | +1 | ns | BLA | (Berlau & McGaugh, 2006) |
| Bicuculline + propanolol | ns | No effect1 | ns | BLA | (Berlau & McGaugh, 2006) |
| FG7142 | − | − | ns | ip | (Harris & Westbrook, 1998) |
| ns | − | ns | ip | (Kim & Richardson, 2007, 2009) | |
| GABAB receptor antagonism | |||||
| GABAB(1b) KO | −5 | ns | ns | No drug | (Jacobson et al., 2006) |
| Phaclofen | ns | No effect | ns | ip | (Heaney et al., 2012) |
| CGP52432 | ns | No effect | ns | po | (Sweeney et al., 2013) |
Drug administration following extinction training;
only cued memory, contextual intact,
trace conditioning,
reconsolidation (injection prior reactivation of memory),
conditioned taste aversion,
midazolam may not impair fear extinction if initial extinction occurs drug-free [see (Hart et al., 2014)],
short extinction training (5 CS presentations),
injection prior renewal-testing.
Reduced fear expression at start of extinction training;
enhanced immobility at start of extinction training;
+, Improved; -, impaired; (+) or (−), only minor effects; ip, intraperitoneal injection; po, peroral administration; ns, not studied; HPC, intra-hippocampal administration; BLA, intra-basolateral amygdala administration; IL, infralimbic cortex; PL, prelimbic cortex; Ren-A, Fear renewal in conditioning context; ag, agonist; ant, antagonist, KO, knock-out;