TABLE 5.

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

ReceptorTypeCompoundDrug of AbuseBehavioral EffectReferences
mGlu1PAMSYN119/Ro0711401CocaineBlocks incubation of cue-induced cocaine craving after extended-access self-administrationLoweth et al., 2014
MethamphetamineNo effect on incubation of methamphetamine craving after extended-access self-administration and withdrawalMurray et al., 2019
NAMJNJ-16259685AlcoholDecreased responding under FR/PR schedulesBesheer et al., 2008a,b
Cocaine and methamphetamineDecreased self-administration under a second-order reinforcement schedule of reinforcement (FI5-FR10)Achat-Mendes et al., 2012
CPCCOEtAlcoholDecreased 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 CPPd1
(See footnotes.)
EMQMCMNicotineInhibited cue and nicotine-induced reinstatement of nicotine-seeking behaviorDravolina et al., 2007
Morphine and cocaineInhibited the expression of locomotor sensitizationDravolina et al., 2006; Kotlinska and Bochenski, 2007
YM298198CocaineDecreased cocaine-primed reinstatement of cocaine seekingSchmidt et al., 2015
mGlu5NAMMPEP/MTEPCocaine, nicotine, heroin, and alcoholAttenuates 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;
CocaineAttenuated cue-induced reinstatement of cocaine seekingBäckström and Hyytiä, 2007; Knackstedt et al., 2014; Knackstedt and Schwendt, 2016
Alcohol, cocaine, and nicotineReduced breakpoints under PR reinforcement schedulePaterson et al., 2003; Besheer et al., 2008b
MethamphetamineReduced incubated methamphetamine seeking; decreased self-administration under FR and PR schedules of reinforcementGass et al., 2009; Murray et al., 2021
Partial NAMM-5MPEP/Br-5MPEPyCocaineDecreased self-administration and attenuated the discriminative stimulus effects of cocaineGould 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.