Work aversion and associated changes in dopamine and serotonin transporter after methamphetamine exposure in rats

Abstract

Rationale Methamphetamine (mAMPH) administration in animals can lead to a variety of cognitive and behavioral deficits. We previously reported non-acute reversal learning impairments after a single-day administration of mAMPH, providing evidence of this drug’s selective effects on inhibitory control. Effortful decision-making (i.e., how much effort to invest in rewards) is an aspect of cognition that has not yet been explored after mAMPH. Objectives Given that frontostriatal circuitry mediating this type of choice is vulnerable to the effects of mAMPH, we tested the hypothesis that mAMPH may also affect decision-making involving effort, another form of cognitive flexibility. Methods We examined the non-acute effects of an experimenter-administered single day of mAMPH on effort discounting. In this task, rats previously treated with mAMPH or saline (SAL) could select a high reward at the cost of climbing over a tall barrier or a low reward with no barrier impeding its procurement. Results Following treatment, mAMPH rats were more work-averse than SAL rats. A control task showed there were no treatment group differences when the high and low rewards involved equal work: all rats chose the high reward preferentially. There were no significant treatment group differences in [125I]RTI-55 binding to dopamine and serotonin transporters (DAT, SERT) in any of the regions assayed; however, there were significant correlations of accumbens DAT and cingulate SERT with post-treatment performance. Conclusions These findings suggest that even modest dose mAMPH exposure has long-lasting effects on effortful decision-making and may do so through influences on forebrain monoaminergic systems.

Long-term effects of exposure to methamphetamine in adolescent rats

“…Food and water were available ad libitum until behavioral testing. Treatment and behavioral testing took place between 0800 and 1600 hours, as previously reported (Izquierdo et al, 2010; Kosheleff et al, 2011). All procedures were in accordance with the Guide for the Care and Use of Laboratory Animals (National Research Council of the National Academies, 2013) and approved by the CSULA Institutional Animal Care and Use Committee.…”

An Evaluation of the Evidence that Methamphetamine Abuse Causes Cognitive Decline in Humans

“…When assessed at least 1 week after MA administration, rats and mice that are administered large, binge doses of MA (X4 mg/kg per dose, often multiple times per day) exhibit deficits in several cognitive domains, including object recognition memory (Belcher et al, 2005;Siegel et al, 2010), odor recognition memory (O'Dell et al, 2011), spatial learning (Acevedo et al, 2007;Vorhees et al, 2009), sequential learning (Chapman et al, 2001;Daberkow et al, 2005), path integration learning (Herring et al, 2008), working memory (Mizoguchi et al, 2011), effort discounting (similar to delay discounting) (Kosheleff et al, 2012), and reversal learning (Izquierdo et al, 2010).…”

Methamphetamine blocks exercise effects on Bdnf and Drd2 gene expression in frontal cortex and striatum

“…Many drugs of abuse, including methamphetamine, exert their reinforcing effects by dramatically increasing dopamine (DA) signaling in the striatum, mimicking the effects of many natural rewards. Neuroplastic changes, especially adaptations in DA receptors and transporters, have been found to contribute to many of the cognitive and behavioral changes that are associated with compulsive drug seeking and addiction (Groman et al, 2013; Kosheleff et al, 2012; Izquierdo et al, 2010). Experience with methamphetamine, therefore, may recalibrate striatal reward circuitry to change reward valuation of and responses to future rewards.…”