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

Abstract

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.

Individual differences in impulsive and risky choice: Effects of environmental rearing conditions

“…This is surprising given the growing evidence of the importance of timing processes in contributing to individual differences in choice behavior (Baumann & Odum, 2012; Galtress et al, 2012; Heilbronner & Meck, 2013; Marshall et al, under review; McClure, Podos, & Richardson, 2014; Smith, Marshall, & Kirkpatrick, under review). However, Galtress et al (2012) suggested that measurements of timing within an impulsive choice task may underestimate individual difference correlations with choice behavior as the choices themselves may impact on timing behavior.…”

Time discounting and time preference in animals: A critical review

“…Using the intertemporal choice task to justify a correspondence can lead to circular reasoning in the absence of other measures of impulsivity. More importantly, no matter the psychological basis of intertemporal choice behavior, it requires unbiased perception and evaluation of the time and reward, and an appropriate trade-off between them; drugs that affect temporal discounting generally also affect the perception and evaluation of both time and drugs (Heilbronner & Meck, 2014). Changes to these processes may spuriously appear to be changes in self-control or impulsivity.…”

“…Thus, animals are used as a model for the neural basis of human cognitive processes (e.g., Hwang, Kim, & Lee, 2009;Louie & Glimcher, 2010). Second, animals can be more readily subjected to techniques that manipulate brain activity, such as optogenetics or psychopharmacology (e.g., Cardinal, Winstanley, Robbins, & Everitt, 2004;Heilbronner & Meck, 2014). Third, techniques devised for animal studies are often used in preverbal humans as a way of studying cognitive development.…”

Clock Speed as a Window into Dopaminergic Control of Emotion and Time Perception

“…Several decades of work has described patients with schizophrenia also suffer from disrupted perceptual timing (Ciullo et al, 2016;Ward et al, 2012). As in Parkinson's disease, several drugs that are effective for schizophrenia (including haloperidol) act on dopaminergic receptors, with some potently blocking striatal D2 signaling and others such as clozapine, risperidone, and aripiprazole with partial action on dopamine receptors in addition to serotonin and norepinephrine receptors (e.g., Buhusi & Meck, 2007;Heilbronner & Meck, 2014;MacDonald & Meck, 2005).…”