TABLE 5.

Summary of preclinical efficacy of group I mGlu receptor allosteric modulators in substance use disorder models

Receptor	Type	Compound	Drug of Abuse	Behavioral Effect	References
mGlu1	PAM	SYN119/Ro0711401	Cocaine	Blocks incubation of cue-induced cocaine craving after extended-access self-administration	Loweth et al., 2014
			Methamphetamine	No effect on incubation of methamphetamine craving after extended-access self-administration and withdrawal	Murray et al., 2019
	NAM	JNJ-16259685	Alcohol	Decreased responding under FR/PR schedules	Besheer et al., 2008a,b
			Cocaine and methamphetamine	Decreased self-administration under a second-order reinforcement schedule of reinforcement (FI5-FR10)	Achat-Mendes et al., 2012
		CPCCOEt	Alcohol	Decreased self-administration under FR and PR schedules of reinforcement in alcohol-preferring P-rats or C57BL/6J mice;a,b,c reduced ethanol reinforcement, consumption, and expression of ethanol CPPd	1 (See footnotes.)
		EMQMCM	Nicotine	Inhibited cue and nicotine-induced reinstatement of nicotine-seeking behavior	Dravolina et al., 2007
			Morphine and cocaine	Inhibited the expression of locomotor sensitization	Dravolina et al., 2006; Kotlinska and Bochenski, 2007
		YM298198	Cocaine	Decreased cocaine-primed reinstatement of cocaine seeking	Schmidt et al., 2015
mGlu5	NAM	MPEP/MTEP	Cocaine, nicotine, heroin, and alcohol	Attenuates self-administration (intravenous or oral)	Ombelet et al., 1994; Kenny et al., 2003, 2005; Paterson et al., 2003; Bäckström et al., 2004; Tessari et al., 2004; Bespalov et al., 2005; Cowen et al., 2005, 2007; Lee et al., 2005; McMillen et al., 2005; Olive et al., 2005; Hodge et al., 2006; Lominac et al., 2006; Liechti and Markou, 2007; Besheer et al., 2008b; Palmatier et al., 2008;
			Cocaine	Attenuated cue-induced reinstatement of cocaine seeking	Bäckström and Hyytiä, 2007; Knackstedt et al., 2014; Knackstedt and Schwendt, 2016
			Alcohol, cocaine, and nicotine	Reduced breakpoints under PR reinforcement schedule	Paterson et al., 2003; Besheer et al., 2008b
			Methamphetamine	Reduced incubated methamphetamine seeking; decreased self-administration under FR and PR schedules of reinforcement	Gass et al., 2009; Murray et al., 2021
	Partial NAM	M-5MPEP/Br-5MPEPy	Cocaine	Decreased self-administration and attenuated the discriminative stimulus effects of cocaine	Gould et al., 2016

CPP, conditioned place preference; FI, fixed interval ;FR, fixed ratio; P, preferring; SYN119, mGlu1 PAM.

^aCasabona et al., 1997.

^bHodge et al., 2006.

^cSchroeder et al., 2005.

^dLominac et al., 2006.