Table 6.
Cannabinoid signaling in fear extinction (preclinical studies).
| Enhanced cannabinoid signaling | |||||
|---|---|---|---|---|---|
| Drug/manipulation | Extnction training |
Extinction retrieval |
Longterm extnction |
Route | Reference |
| Cannabidiol | + | + | ns | icv | (Bitencourt et al., 2008) |
| + | + | ns | IL | (Do Monte et al., 2013) | |
| Anandamide | ns | +1 | ns | dCA1 | (de Oliveira Alvares et al., 2008) |
| AM404 (eCB uptake inhibitor) | ns | + | ns | ip | (Pamplona et al., 2008) |
| ns | + | + (Re-in) | ip | (Chhatwal et al., 2005b) | |
| + | (+) | ns | icv | (Bitencourt et al., 2008) | |
| No training | + | ns | IL | (Lin et al., 2009) | |
| AM3506 (FAAH inhibitor) | ns | + | ns | ip | (Gunduz-Cinar et al., 2013b) |
| WIN 55,212-2 (low-dose CB1 Ag) | +* | No effect2 | ns | ip | (Pamplona et al., 2006) |
| WIN 55,212-2 (high-dose CB1 Ag) | (−)* | No effect2 | ns | ip | (Pamplona et al., 2006) |
| WIN 55,212-2 (CB1 Ag) | +° | +° | ns | ip | (Pamplona et al., 2006) |
| ns | + | nd | ip | (Pamplona et al., 2008) | |
| WIN 55,212-2 (CB1 Ag) | ns | +4 | ns | BLA | (Ganon-Elazar & Akirav, 2013)) |
| ns | +4 | ns | HPC | (Ganon-Elazar & Akirav, 2013) | |
| ns | No effect4 | ns | mPFC | (Ganon-Elazar & Akirav, 2013) | |
| ns | + | No effect (Re-in, SR3) | IL | (Lin et al., 2009) | |
| No training | + | ns | IL | (Lin et al., 2009) | |
| ns | No effect | ns | PL | (Kuhnert et al., 2013) | |
| HU210 | No training | + | ns | IL | (Lin et al., 2009) |
| URB597 (AEA hydrolysis inhibitor) | No training | + | ns | IL | (Lin et al., 2009) |
| AM3506 (FAAH inhibitor) + SR141716A (CB1 ant) |
ns | No effect | ns | ip + BLA | (Gunduz-Cinar et al., 2013b) |
| AM3506 (FAAH inhibitor) | ns | + | ns | BLA | (Gunduz-Cinar et al., 2013b) |
| No training | No effect | ns | BLA | (Gunduz-Cinar et al., 2013b) | |
| Cannabidiol + SR141716A (CB1 ant) | No effect | No effect | ns | IL + ip | (Do Monte et al., 2013) |
| Reduced cannabinoid signaling | |||||
| Drug/manipulation | Extnction learning |
Extinction retrieval | Longterm extinction | Administration route | Reference |
| CB1 KO | − | − | ns | No drug | (Cannich et al., 2004) |
| CB1 KO | − | ns | ns | No drug | ((Dubreucq et al., 2010); (Kamprath et al., 2006); (Marsicano et al., 2002); (Plendl & Wotjak, 2010)) |
| D1-CB1 KO | − | ns | ns | No drug | (Terzian et al., 2011) |
| SR141716A CB1 ant | ns | No effect1 | ns | sc | (Marsicano et al., 2002) |
| − | ns | ns | sc, ip | ((Kamprath et al., 2006); (Niyuhire et al., 2007); (Plendl & Wotjak, 2010) |
|
| ns | −1 | ns | ip | (Suzuki et al., 2004) | |
| − | No effect | ns | ip | (Pamplona et al., 2006, 2008) | |
| ns | − | ns | ip | (Chhatwal et al., 2005b) | |
| −## | No effect | ns | ip | (Bowers & Ressler, 2015) | |
| AM251 (CB1 inverse ag) | − | ns | ns | ip | (Reich et al., 2008) |
| ns | −1 | ns | dCA1 | (de Oliveira Alvares et al., 2008) | |
| ns | − | ns | IL | (Lin et al., 2009) | |
| No training | No effect | ns | IL | (Lin et al., 2009) | |
| ns | − | ns | PL | (Kuhnert et al., 2013) | |
1
Drug administration following extinction training;
2
drug-free retrieval of contextual fear memory;
3
5 days,
4
single-prolonged-stress model: injection immediately after trauma.
*
Recent memory;
°
remote memory;
##
enhanced immobility at start of extinction training;
+, Improved; -, impaired; (+) or (−), only minor effects; ip, intraperitoneal injection; ip, sc, subcutanous injection; ns, not studied; HPC, intra-hippocampal administration; BLA, intra-basolateral amygdala administration; IL, infralimbic cortex; PL, prelimbic cortex; CA1, cornu ammonis 1; Re-in, reinstatement; SR, spontaneous recovery, ag, agonist; ant, antagonist, KO, knock-out;