Dissociable effects of mGluR5 allosteric modulation on distinct forms of impulsivity in rats: interaction with NMDA receptor antagonism

Abstract

These findings demonstrate that mGluR5 allosteric modulation selectively dissociates motor and choice impulsivity. We further show that mGluR5 PAMs may have therapeutic utility in selectively targeting specific aspects of impulsivity and executive dysfunction.

Effects of Group I metabotropic glutamate receptor antagonists on sensitivity to reinforcer magnitude and delayed reinforcement in a delay-discounting task in rats: Contribution of delay presentation order

“…To prevent the ceiling effect observed with A parameter estimates, future studies can use a concurrent-chains procedure, in which animals cannot respond exclusively for the LR during any block of trials [see 17 for a discussion of this procedure]. Overall, the current results, in conjunction with previous results [10], show that mGluR 5 receptors do not mediate sensitivity to reinforcer magnitude or sensitivity to delayed reinforcement.…”

“…To our knowledge, only two studies have focused on the contribution of Group I mGluRs in impulsive choice, with results showing that an mGluR 1 antagonist decreases impulsive choice [9], whereas mGluR 5 allosteric modulators do not alter impulsive choice [10]. Although previous studies have examined the contribution of Group I mGluRs in discounting, they have not examined the effects of mGluR ligands in mediating sensitivity to reinforcer magnitude (i.e., how much an animal responds for the large reinforcer (LR) when its delivery is immediate; see 6 for a full discussion of what this parameter measures) and sensitivity to delayed reinforcement (i.e., what is typically considered to be impulsive choice), two parameters that influence an animal’s discounting [11].…”

Selective and interactive effects of D 2 receptor antagonism and positive allosteric mGluR4 modulation on waiting impulsivity

“…Although the task was sufficiently sensitive to detect the expected impulsivity-reducing effects of d-amphetamine, the conclusion that Cpd11 reduces choice impulsivity requires replication as control animals appeared to show an unexpectedly steep rate of discounting at 2 s. Indeed in our recent study preference for the delayed reward was higher in control rats at this delay (Isherwood et al., 2015). Nevertheless, the apparently opposing effect of Cpd11 on motor and choice impulsivity is consistent with studies demonstrating that lesions of the STN produce similarly opposing effects on motor and choice impulsivity (Baunez and Robbins, 1997, Uslaner and Robinson, 2006, Winstanley et al., 2005).…”

Effects of N-methyl-D-aspartate receptor ligands on sensitivity to reinforcer magnitude and delayed reinforcement in a delay-discounting procedure

“…In the current experiment, impulsive choice was measured with a behavioral task employing a concurrent schedule of reinforcement (e.g., Evenden and Ryan 1996), which has been used consistently during the past 20 years (e.g., Baarendse and Vanderschuren 2012; Cardinal et al 2000; Floresco et al 2008; Fox et al 2008; Higgins et al 2016; Isherwood et al 2015; Koffarnus et al 2011; Liu et al 2004; Slezak and Anderson 2009; Simon et al 2007; Stanis et al 2008; Sukhotina et al 2008; van Gaalen et al 2006; Winstanley et al 2005, 2007; Yates et al 2015). Because delay discounting is influenced by both reinforcer magnitude and delay (Ho et al 1999), the exponential discounting function was used to determine how NMDA receptor ligands affect sensitivity to these parameters.…”