Effects of acute administration of nicotinic and muscarinic cholinergic agonists and antagonists on performance in different cost–benefit decision making tasks in rats

Mendez, Ian A.; Gilbert, Ryan J.; Bizon, Jennifer L.; Setlow, Barry

doi:10.1007/s00213-012-2777-y

Cited by 47 publications

(51 citation statements)

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“…For example, MK-801 inhibits nicotinic acetylcholine receptors (Amador and Dani 1991); however, blockade of nicotinic receptors does not alter discounting of delayed or probabilistic reinforcement (Mendez et al 2012). As for dopamine activity, previous work has shown that acute administration of MK-801 (0.03 and 0.1 mg/kg) increases dopamine levels in prefrontal cortex (Tsukada et al 2005).…”

Section: Discussionmentioning

confidence: 99%

Role of ionotropic glutamate receptors in delay and probability discounting in the rat

et al. 2014

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Rationale Discounting of delayed and probabilistic reinforcement is linked to increased drug use and pathological gambling. Understanding the neurobiology of discounting is important for designing treatments for these disorders. Glutamate is considered to be involved in addiction-like behaviors; however, the role of ionotropic glutamate receptors (iGluRs) in discounting remains unclear. Objectives The current study examined the effects of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) glutamate receptor blockade on performance in delay and probability discounting tasks. Methods Following training in either delay or probability discounting, rats (n = 12, each task) received pretreatments of the NMDA receptor antagonists MK-801 (0, 0.01, 0.03, 0.1, or 0.3 mg/kg, s.c.) or ketamine (0, 1.0, 5.0, or 10.0 mg/kg, i.p.), as well as the AMPA receptor antagonist CNQX (0, 1.0, 3.0, or 5.6 mg/kg, i.p.). Hyperbolic discounting functions were used to estimate sensitivity to delayed/probabilistic reinforcement and sensitivity to reinforcer amount. Results An intermediate dose of MK-801 (0.03 mg/kg) decreased sensitivity to both delayed and probabilistic reinforcement. In contrast, ketamine did not affect the rate of discounting in either task but decreased sensitivity to reinforcer amount. CNQX did not alter sensitivity to reinforcer amount or delayed/probabilistic reinforcement. Conclusions These results show that blockade of NMDA receptors, but not AMPA receptors, decreases sensitivity to delayed/probabilistic reinforcement (MK-801) and sensitivity to reinforcer amount (ketamine). The differential effects of MK-801 and ketamine demonstrate that sensitivities to delayed/probabilistic reinforcement and reinforcer amount are pharmacologically dissociable.

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Section: Discussionmentioning

confidence: 99%

Role of ionotropic glutamate receptors in delay and probability discounting in the rat

et al. 2014

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“…Probability-discounting data are often analyzed by applying a two-way ANOVA to the proportion of responses for the probabilistic reinforcer (Boutros et al, 2014; Ghods-Sharifi et al, 2009; Mendez et al, 2012; Rokosik and Napier, 2012; Schindler et al, 2014; St. Onge and Floresco, 2009, 2010; St.…”

Section: Methodsmentioning

confidence: 99%

Effects of NMDA receptor antagonists on probability discounting depend on the order of probability presentation

Yates

Breitenstein

Gunkel

et al. 2016

Pharmacology Biochemistry and Behavior

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Risky decision making can be measured using a probability-discounting procedure, in which animals choose between a small, certain reinforcer and a large, uncertain reinforcer. Recent evidence has identified glutamate as a mediator of risky decision making, as blocking the N-methyl-D-aspartate (NMDA) receptor with MK-801 increases preference for a large, uncertain reinforcer. Because the order in which probabilities associated with the large reinforcer can modulate the effects of drugs on choice, the current study determined if NMDA receptor ligands alter probability discounting using ascending and descending schedules. Sixteen rats were trained in a probability-discounting procedure in which the odds against obtaining the large reinforcer increased (n = 8) or decreased (n = 8) across blocks of trials. Following behavioral training, rats received treatments of the NMDA receptor ligands MK-801 (uncompetitive antagonist; 0, 0.003, 0.01, or 0.03 mg/kg), ketamine (uncompetitive antagonist; 0, 1.0, 5.0, or 10.0 mg/kg), and ifenprodil (NR2B-selective non-competitive antagonist; 0, 1.0, 3.0, or 10.0 mg/kg). Results showed discounting was steeper (indicating increased risk aversion) for rats on an ascending schedule relative to rats on the descending schedule. Furthermore, the effects of MK-801, ketamine, and ifenprodil on discounting were dependent on the schedule used. Specifically, the highest dose of each drug decreased risk taking in rats in the descending schedule, but only MK-801 (0.03 mg/kg) increased risk taking in rats on an ascending schedule. These results show that probability presentation order modulates the effects of NMDA receptor ligands on risky decision making.

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“…No additional shaping was needed prior to testing in the delay-discounting task, as it was similar in design to the RDT. A detailed description of this task is provided in Mendez et al (2012). Each 60 min session consisted of 5 blocks of 12 trials each.…”

Section: Methodsmentioning

confidence: 99%

Affective and cognitive mechanisms of risky decision making

Shimp

Mitchell

Beas

et al. 2015

Neurobiology of Learning and Memory

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The ability to make advantageous decisions under circumstances in which there is a risk of adverse consequences is an important component of adaptive behavior; however, extremes in risk taking (either high or low) can be maladaptive and are characteristic of a number of neuropsychiatric disorders. To better understand the contributions of various affective and cognitive factors to risky decision making, cohorts of male Long-Evans rats were trained in a “Risky Decision making Task” (RDT), in which they made discrete trial choices between a small, “safe” food reward and a large, “risky” food reward accompanied by varying probabilities of footshock. Experiment 1 evaluated the relative contributions of the affective stimuli (i.e., punishment vs. reward) to RDT performance by parametrically varying the magnitudes of the footshock and large reward. Varying the shock magnitude had a significant impact on choice of the large, “risky” reward, such that greater magnitudes were associated with reduced choice of the large reward. In contrast, varying the large, “risky” reward magnitude had minimal influence on reward choice. Experiment 2 compared individual variability in RDT performance with performance in an attentional set shifting task (assessing cognitive flexibility), a delayed response task (assessing working memory), and a delay discounting task (assessing impulsive choice). Rats characterized as risk averse in the RDT made more perseverative errors on the set shifting task than did their risk taking counterparts, whereas RDT performance was not related to working memory abilities or impulsive choice. In addition, rats that showed greater delay discounting (greater impulsive choice) showed corresponding poorer performance in the working memory task. Together, these results suggest that reward-related decision making under risk of punishment is more strongly influenced by the punishment than by the reward, and that risky and impulsive decision making are associated with distinct components of executive function.

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Effects of acute administration of nicotinic and muscarinic cholinergic agonists and antagonists on performance in different cost–benefit decision making tasks in rats

Cited by 47 publications

References 46 publications

Role of ionotropic glutamate receptors in delay and probability discounting in the rat

Role of ionotropic glutamate receptors in delay and probability discounting in the rat

Effects of NMDA receptor antagonists on probability discounting depend on the order of probability presentation

Affective and cognitive mechanisms of risky decision making

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