Table 1.

Effects of endocannabinoid system (ECS) manipulations on fear expression (the fear response to the first conditioned stimulus (CS)/context-exposure after conditioning)

Type	Timing	Site	Paradigm	Presessions	Fear expression after manipulation		Reference
					Observed effect of injection/knockout	Postulated effect of ECS activation
Cued	Pre-train	Systemic	Auditory FC	Different contextse	AM251, AM4113 reduce	Increase	Sink et al. (2010)
		Systemic	Olfactory FC	Both contexts	AM251 reduces	Increase	Tan et al.(2010)
		BLA & PL	Olfactory FC	Both contexts	AM251 reducesa	Increase	Tan et al. (2010)
		mPFC	Olfactory FC	Both contexts	WIN55,212-2 increases; AM251 reduces	Increase	Laviolette and Grace (2006)
		Systemic	Auditory FC	No	AM251 increases	Reduction	Arenos et al. (2006)
		Systemic	Auditory FC	No	AM251 increases	Reduction	Reich et al. (2008)
	Pre-test	Systemic	Auditory FC	No	AM251 increases	Reduction	Arenos et al. (2006)
		Systemic	Auditory FC	No	AM251 increases	Reduction	Reich et al. (2008)
		CeA	Auditory FC	No	AM251 increases	Reduction	Kamprath et al. (2011)
		IL	Visual FC	Conditioning context	WIN55,212-2, AM404, URB597, HU-210 reduce	Reduction	Lin et al. (2009)
	Knockout	Complete	Auditory FC	No	TRPV1 ko reduces	Reduction	Marsch et al. (2007)
Spatial	Pre-train	Systemic	Contextual FC	No	AM251 reduces	Increase	Arenos et al. (2006)
		Systemic	Contextual FC	Different contextse	AM251 increases	Reduction	Sink et al. (2010)
		Systemic	Contextual FC	No	WIN55,212-2 reduces	Reduction	Pamplona and Takahashi (2006)
		BLA	Inhibitory avoidance	No	AM251 increases	Reduction	Ganon-Elazar and Akirav (2009)
	Post-train	BLA	Inhibitory avoidance	No	WIN55,212-2 increases; AM251 reduces	Increase	Campolongo et al. (2009)
		Hippocampus	Inhibitory avoidance	No	AEA increases, AM251 reduces	Increase	de Oliveira Alvares et al. (2008b)
		Hippocampus	Contextual FC	No	AM251 reducesb	Increase	de Oliveira Alvares et al. (2010)
		Systemic	Contextual FC	No	HU-210 reduces	Reduction	Mackowiak et al. (2009)
	Pre-test	Systemic	Contextual FC	No	AM251 reduces	Increase	Arenos et al. (2006)
		Systemic	Contextual FC	No	URB597 increases (in presence of pain)	Increase	Butler et al. (2008)
		Systemic	Contextual FC	No	WIN55,212-2 increases; AM251 reduces	Increase	Mikics et al. (2006)
		Systemic	Contextual FC	No	WIN55,212-2 reduces/increasesc	Reductiond	Pamplona et al. (2006)
		BLA	Contextual FC	No	SR141716 increases (in presence of pain)	Reduction	Roche et al. (2007)
		BLA	Inhibitory avoidance	No	AM404 lower; AM251 increases	Reduction	Ganon-Elazar and Akirav (2009)
		Hippocampus	Inhibitory avoidance	No	AM251 increases	Reduction	de Oliveira Alvares et al. (2008b)
		IL	Contextual FC	Conditioning context	AEA, AM404 reduces; AM251 increases	Reduction	Lisboa et al. (2010)
		PAG	Contextual FC	Conditioning context	AEA, AM404 reduces	Reduction	Resstel et al. (2008)
	Knockout	Complete	Contextual FC	No	CB1 receptor ko reduces	Increase	Mikics et al. (2006)
		Complete	Barnes maze	No	FAAH ko increases, blocked by SR141716	Increase	Wise et al. (2009)

In paradigms that test fear expression after ECS manipulation, the type of paradigm (cued vs spatial), time point of manipulation (chronic (knockout), pre-training, post-training, pre-test), site of injection (systemic, various brain areas) and the use or lack of pre-conditioning adaptation sessions can explain part, but not all, of the variation in outcomes. The postulated effect of ECS activation on fear expression (column 7) is derived from the effects of ECS manipulations; studies that reported no effect are not included in this table.

^aHalf the dose in PL-only or BLA-only produced no effect; ^bwith a strong shocking protocol, or with a weaker shocking protocol only after previous stress; ^creduction after a low dose, increase after a high dose; ^dat a low dose; ^eincluding neither the conditioning context nor the extinction context.

BLA: basolateral amygdale, CeA: central amygdale, FC: fear conditioning, IL: infralimbic cortex, ko: knockout, mPFC: medial prefrontal cortex, PAG: periaqueductal gray, PL: prelimbic cortex.