Pharmacological manipulations of interval timing using the peak procedure in male C3H mice

Balcı, Fuat; Ludvig, Elliot Andrew; Gibson, Jacqueline M.; Allen, Bruce C.; Frank, Krystal M.; Kapustinski, Bryan J.; Fedolak, Thomas E.; Brunner, Daniela

doi:10.1007/s00213-008-1248-y

Cited by 52 publications

(50 citation statements)

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“…Though we did not observe a clear leftward shift in peak times for all rats, some rats did show substantial disruption in timing that may have been the result of a combination of increased peak width and a leftward shift in the 10-s and 40-s PI functions, as illustrated in Fig. 11 (see Balci et al, 2008, 2009; Cheng et al, 2007c). By collapsing across COC and MAP sessions, we saw a strong trend toward an increase in the peak width for the 10-s target duration which is quite evident in Fig.…”

Section: Resultsmentioning

confidence: 62%

Dissociations between interval timing and intertemporal choice following administration of fluoxetine, cocaine, or methamphetamine

Heilbronner

Meck

2014

Behavioural Processes

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The goal of our study was to characterize the relationship between intertemporal choice and interval timing, including determining how drugs that modulate brain serotonin and dopamine levels influence these two processes. In Experiment 1, rats were tested on a standard 40-s peak-interval procedure following administration of fluoxetine (3, 5, or 8 mg/kg) or vehicle to assess basic effects on interval timing. In Experiment 2, rats were tested in a novel behavioral paradigm intended to simultaneously examine interval timing and impulsivity. Rats performed a variant of the bi-peak procedure using 10-s and 40-s target durations with an additional “defection” lever that provided the possibility of a small, immediate reward. Timing functions remained relatively intact, and ‘patience’ across subjects correlated with peak times, indicating a negative relationship between ‘patience’ and clock speed. We next examined the effects of fluoxetine (5 mg/kg), cocaine (15 mg/kg), or methamphetamine (1 mg/kg) on task performance. Fluoxetine reduced impulsivity as measured by defection time without corresponding changes in clock speed. In contrast, cocaine and methamphetamine both increased impulsivity and clock speed. Thus, variations in timing may mediate intertemporal choice via dopaminergic inputs. However, a separate, serotonergic system can affect intertemporal choice without affecting interval timing directly.

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Section: Resultsmentioning

confidence: 62%

Dissociations between interval timing and intertemporal choice following administration of fluoxetine, cocaine, or methamphetamine

Heilbronner

Meck

2014

Behavioural Processes

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“…Given the ubiquity of timing as a cognitive domain (ranging from fish to humans), the use of a temporal discrimination paradigm (thus temporal information processing) as the context for decision-making under uncertainty adds a translational character to our decision-making task. The translational nature of this cognitive domain has started to receive increasing appreciation in preclinical research (20)(21).…”

Section: Discussionmentioning

confidence: 99%

Risk assessment in man and mouse

Balcı

Freestone

Gallistel

2009

Proc. Natl. Acad. Sci. U.S.A.

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Human and mouse subjects tried to anticipate at which of 2 locations a reward would appear. On a randomly scheduled fraction of the trials, it appeared with a short latency at one location; on the complementary fraction, it appeared after a longer latency at the other location. Subjects of both species accurately assessed the exogenous uncertainty (the probability of a short versus a long trial) and the endogenous uncertainty (from the scalar variability in their estimates of an elapsed duration) to compute the optimal target latency for a switch from the short- to the long-latency location. The optimal latency was arrived at so rapidly that there was no reliably discernible improvement over trials. Under these nonverbal conditions, humans and mice accurately assess risks and behave nearly optimally. That this capacity is well-developed in the mouse opens up the possibility of a genetic approach to the neurobiological mechanisms underlying risk assessment.

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“…The nicotinic acetylcholine receptor agonist nicotine, muscarinic acetylcholine receptor antagonist scopolamine, the 5-HT 2C antagonist SB242084, and two N -methyl-D-aspartate (NMDA) receptor antagonists, Ro 63-1908 and dizoclipine all increase premature responding in the 5-CSRTT (Day et al, 2007; Jones & Higgins, 1995; Pattij et al 2007, Fletcher at al., 2007; Higgins et al, 2003a; Higgins et al 2003b). Predictably, all of these agents speed temporal perception across an array of timing analyses (Meck, 2007; Soffie & Lejeune, 1992; Balci et al, 2008; Body et al, 2014; Higgins et al, 2003b; Sanger, 1992). Hence, pharmacological agents that increase premature responses also speed temporal perception.…”

Section: Discussionmentioning

confidence: 99%

“…Atomoxetine decreased premature responses in the 5-CSRTT when a long-ITI challenge was used in rats (Navarra et al, 2008). On the peak interval-timing task, atomoxetine dose dependently reduced variability in response rates in rats, meaning their timing had not sped up or slowed down overall, but rather had become more precise (Balci et al, 2008). Increased timing precision on the 5-CSRTT could explain the decrease in premature responding in the absence of an overall slowing of response speed since the animals adapted quicker to the longer ITI challenge.…”

Section: Discussionmentioning

confidence: 99%

Premature responses in the five-choice serial reaction time task reflect rodents’ temporal strategies: evidence from no-light and pharmacological challenges

et al. 2016

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Rationale The five-choice serial reaction time task (5-CSRTT) is regularly used to study attention and impulsivity. In the 5-CSRTT, rodents initiate a trial, then after an inter-trial interval (ITI), a light appears in one of five holes. Responding in the lit vs. unlit hole reflects attention (accuracy), while responding prematurely before a light appears is suggested to reflect impulsivity/response disinhibition. Comparison of rat and mouse 5-CSRTT performance has raised questions on the validity of premature responses as measuring impulsivity/response inhibition. To minimize effort, rodents may use a temporal strategy, enabling their ‘timing’ of the ITI, minimizing the need to attend during this delay. Greater reliance this strategy could result in premature responses due to “guesses” if their timing was poor/altered. Objectives To assess the degree to which rats and/or mice utilize a temporal strategy, we challenged performance using infrequent no-light trials during 5-CSRTT performance. Results Even when no light appeared when one was expected, rats responded ~60% compared to ~40% in mice, indicating a greater reliance on a temporal strategy by rats than by mice. Consistent with this hypothesis, rats made more premature responses than mice. Additional studies using a temporal discrimination task and a 5-CSRTT variant demonstrated that delta-9-tetrahydrocannabinol, the active ingredient in cannabis, slowed temporal perception and reduced premature responses. Conclusions These data provide behavioral and pharmacological evidence indicating that premature responses are heavily influenced by temporal perception. Hence, they may reflect an aspect of waiting impulsivity, but not response disinhibition, an important distinction for translational clinical research.

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Pharmacological manipulations of interval timing using the peak procedure in male C3H mice

Abstract: Our results suggest that interval timing has potential as an assay for generalized cognitive performance and that the dopamine-clock hypothesis needs further refinement.

Cited by 52 publications

References 86 publications

Dissociations between interval timing and intertemporal choice following administration of fluoxetine, cocaine, or methamphetamine

Dissociations between interval timing and intertemporal choice following administration of fluoxetine, cocaine, or methamphetamine

Risk assessment in man and mouse

Premature responses in the five-choice serial reaction time task reflect rodents’ temporal strategies: evidence from no-light and pharmacological challenges

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