Table 1.

List of novel pharmacological targets explored for development of innovative treatments in addiction.

Target	Pharmacological Tool	Drug of Abuse	Experimental Procedure	Key Finding	Reference
PPARγ	Pioglitazone, Rosiglitazone	Alcohol	SA, stress-induced reinstatement	reduce	(Stopponi et al., 2011)
	Pioglitazone	Heroin	SA	reduce	(de Guglielmo et al., 2015)
	15-deoxy-delta(12,14)- prostaglandin J(2), Ciglitazone	Nicotine	PPARγ gene expression	increase	(Amoruso et al., 2007)
	Pioglitazone	Morphine	tolerance	reduce	(de Guglielmo et al., 2015)
PPARα	Fenofibrate, Tesaglitazar, Bezafibrate	Alcohol	SA	reduce	(Blednov et al., 2015)
	Clofibrate, WY14643, methyl oleoylethanolamide	Nicotine	SA, cue-, priming- induced reinstatement	reduce	(Panlilio et al., 2012) (Mascia et al., 2011)
PDE4	Rolipram	Alcohol	SA	reduce	(Wen et al., 2012)
	Rolipram	Morphine	withdrawal, tolerance, CPP	reduce	(Itoh et al., 1998) (Nunez et al., 2009) (Thompson et al., 2004)
	Rolipram	Cocaine	CPP, locomotor sensitisation, SA	reduce	(Thompson et al., 2004) (Janes et al., 2009) (Knapp et al., 1999)
PDE10A	MP-10	Alcohol	SA	reduce	(Logrip et al., 2014)
	MP-10	Morphine	CPP	reduce	(Mu et al., 2014)
	Papaverine	Cocaine	CPP	reduce	(Liddie et al., 2012)
CREB	KO mice, antisense oligonucleotide	Morphine	Withdrawal	reduce	(Maldonado et al., 1996) (Lane-Ladd et al., 1997)
	Over-expression	Cocaine	SA	increase	(Carlezon et al., 1998) (Barrot et al., 2002) (Larson et al., 2011) (Bilbao et al., 2014)
	Dominant-negative CREB variant		CPP Priming-induced reinstatement
CRF1R	CRA1000 MTIP MPZP LWH-63 Antalarmin KO mice D-Phe-CRF(12-41)	Alcohol	withdrawal, SA	reduce	(Knapp et al., 2004) (Gehlert et al., 2007) (Sommer et al., 2008) (Sabino et al., 2006) (Chu et al., 2007) (Funk et al., 2007) (Gilpin et al., 2008) (Richardson et al., 2008)
	D-phe CRF(12-41) Antalarmin MPZP	Cocaine	Withdrawal, SA	reduce	(Basso et al., 1999) (Specio et al., 2008)
	alpha-helical CRF(9-41) MPZP	Nicotine	Withdrawal, SA	reduce	(Tucci et al., 2003) (George et al., 2007)
	MPZP MJL-1-109-2 R121919	Heroin	Withdrawal, SA	reduce	(Park et al., 2013) (Greenwell et al., 2009)
NOP	N/OFQ Ro 64-6198	Alcohol	CPP, SA, withdrawal	reduce	(Ciccocioppo et al., 1999) (Kuzmin et al., 2003) (Ciccocioppo et al., 2004) (Martin-Fardon et al., 2000) (Economidou et al., 2011)
	N/OFQ	Morphine	CPP	reduce	(Ciccocioppo et al., 2000) (Murphy et al., 1999)
	N/OFQ	Cocaine Amphetamine	CPP	reduce	(Kotlinska et al., 2002) (Zhao et al., 2003)
OX1	SB-334867	Alcohol	cue-, stress-induced reinstatement	reduce	(Lawrence et al., 2006) (Richards et al., 2008)
	SB-334867	Cocaine	cue-, stress-induced reinstatement	reduce	(Smith et al., 2009) (Boutrel et al., 2005)
	SB-334867	Morphine	cue-induced reinstatement	reduce	(Harris et al., 2005)
NPSR	NPS	Alcohol	SA	no effect	(Cannella et al., 2009) (Ruggeri et al., 2010)
			cue-induced reinstatement	increase
			withdrawal	reduce
	NPS	Morphine	CPP	reduce	(Li et al., 2009)
	NPS SHA 68 NPSR-QA1	Cocaine	SA, CPP	no effect	(Kallupi et al., 2010) (Kallupi et al., 2013) (Cannella et al., 2013)
	SHA 68 NPSR-QA1 [D-Cys(tBu)5 ]NPS		cue-induced reinstatement	reduce
NK1R	KO mice, L822429	Alcohol	SA, CPP, stress-induced reinstatement	reduce	(George et al., 2008) (Thorsell et al., 2010) (Schank et al., 2011)
	KO mice	Morphine	SA, CPP	reduce	(Murtra et al., 2000) (Ripley et al., 2002)
	KO mice	Cocaine	SA, CPP, locomotor sensitisation	no effect	(Ripley et al., 2002)

Abbreviations: Peroxisome proliferating activator receptors gamma (PPARγ), peroxisome proliferating activator receptors alpha (PPARα), cAMP response element-binding protein (CREB), phosphodiesterase 4 (PDE4), phosphodiesterase 10A (PDE10A), corticotropin-releasing factor receptor 1 (CRF1R), nociceptin opioid receptor (NOP), hypocretin-1/orexin A receptor (Ox1), neuropeptide S receptor (NPSR), neurokinin 1 receptor (NK1R), operant self-administration (SA), conditioned place preference (CPP).