Effects of N-methyl-d-aspartate receptor (NMDAr) uncompetitive antagonists in a delay discounting paradigm using a concurrent-chains procedure

Abstract

Impulsive choice is often assessed in rodents using a delay discounting (DD) paradigm in which the delay to a large reinforcer (LR) increases across the session. This procedure allows one to test the effects of pharmacological manipulations within a single session. Because discounting is influenced by sensitivity to reinforcer magnitude (SRM) and sensitivity to delayed reinforcement (SDR), applying quantitative analyses (e.g., fitting hyperbolic function) is important for determining the precise behavioral mechanisms being altered following drug administration. One caveat to this approach is that observing increases in SMR/SDR can be difficult (e.g., most rats choose the LR when its delivery is immediate, whereas some rats may show exclusive preference for the small reinforcer [SR] when a delay on the LR is imposed). We utilized a variant of a concurrent-chains procedure in which rats (n = 8) could not show exclusive preference for either reinforcer, thus allowing one to observe increases/decreases in responding at each delay. The NMDAr antagonists MK-801 (0, 0.003, 0.01, 0.03 mg/kg), ketamine (0, 1.0, 5.0, 10.0 mg/kg), and memantine (0, 2.5, 5.0, 7.5 mg/kg) were administered following baseline training because this receptor has recently been implicated in DD. MK-801 (0.03 mg/kg) decreased SRM and SDR. Memantine (7.5 mg/kg) decreased SRM only. These results show that this variant of the concurrent-chains procedure can be used to study the effects of pharmacological manipulations on distinct aspects of DD.

Using a dependent schedule to measure risky choice in male rats: Effects of d-amphetamine, methylphenidate, and methamphetamine.

“…Considering that nonreinforced responses during the terminal link were not altered by amphetamine/ methamphetamine, one may argue that the drug effects observed in the current study are unrelated to perseverative responding. As discussed in Yates, Gunkel, et al (2018), there is one caveat to this argument. Because rats had to break a photobeam in the food tray to extend the levers in the chamber during the initial link, they were equidistant to each lever at the beginning of each trial.…”

“…A dependent schedule was used to assess risky choice. Specifically, a variant of a concurrent-chains procedure was used (see Figure 1 for a schematic of the procedure; Aparicio et al, 2013Aparicio et al, , 2015Aparicio et al, , 2019Beeby & White, 2013;Pope et al, 2015;Yates, Gunkel, et al, 2018). Each session consisted of five blocks of 10 trials (50 total trials; note: each rat completed all 50 trials following each dose of each drug, with the exception that two rats failed to complete a single trial following administration of the highest dose of methamphetamine) and began with illumination of one of several stimuli (first block of trials: house light; second block: house light and left stimulus light; third block: house light and right stimulus light; fourth block: house light and both stimulus lights; fifth block: both stimulus lights only).…”

“…Responses on the other lever were recorded but had no programmed consequences. Similar to previous research examining dependent schedules within the context of delay discounting (Aparicio et al, 2013(Aparicio et al, , 2015(Aparicio et al, , 2019Beeby & White, 2013;Pope et al, 2015;Yates, Gunkel, et al, 2018), the lever that allowed the rat to advance to the terminal link was pseudorandomized across trials (this is the dependent schedule). For example, during the first trial, the right lever may be designated as "active" for some rats.…”

“…On the second trial, responding on the lever associated with the small, certain reinforcer has no programmed consequences, whereas responding on the lever associated with the large, uncertain reinforcer advances the session (see Figure 1 for a schematic of the dependent schedule used in the current experiment). Dependent schedules have been used to study sensitivity to delayed reinforcement, often in the form of a concurrent-chains procedure (Aparicio, Elcoro, & Alonso-Alvarez, 2015; Aparicio, Hennigan, Mulligan, & Alonso-Alvarez, 2019; Aparicio, Hughes, & Pitts, 2013; Beeby & White, 2013; Maguire, Rodewald, Hughes, & Pitts, 2009; Pitts, Cummings, Cummings, Woodcock, & Hughes, 2016; Pope, Newland, & Hutsell, 2015; Ta, Pitts, Hughes, McLean, & Grace, 2008; Yates, Gunkel, et al, 2018). In a concurrent-chains schedule, each trial is composed of an initial link and a terminal link.…”

A method for studying reinforcement factors controlling impulsive choice for use in behavioral neuroscience

“…Indeed, numerous studies indicate that response allocation in the initial links by pigeons is exquisitely controlled by the reinforcement parameters arranged in the terminal links. Although concurrent-chains procedures have been used with rodents (e.g., Aparicio et al, 2013Aparicio et al, , 2016Aparicio et al, , 2019Ito & Asaki, 1982;Johnson et al, 2013;Orduña et al, 2013;Yates et al, 2018Yates et al, , 2020, this literature is much less extensive than with pigeons. Furthermore, there is lab lore suggesting that choice in rodents does not come under control of within-session changes in reinforcement parameters as readily as choice does in pigeons (e.g., Kyonka, personal communication; we have not been as successful with rats as we have been with pigeons).…”