title: Work aversion and associated changes in dopamine and serotonin transporter after methamphetamine exposure in rats.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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 [(125)I]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.
authors.affiliation: Department of Psychology, California State University, Los Angeles, 5151 State University Drive, Los Angeles, CA 90032, USA.
authors.forename: Alisa R
authors.initials: AR
authors.lastname: Kosheleff
authors.forename: Millie
authors.initials: M
authors.lastname: Grimes
authors.forename: Steve J
authors.initials: SJ
authors.lastname: O'Dell
authors.forename: John F
authors.initials: JF
authors.lastname: Marshall
authors.forename: Alicia
authors.initials: A
authors.lastname: Izquierdo
mesh_terms: D000818:Animals; D003042:Cocaine / Q000031:analogs & derivatives; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D003657:Decision Making / Q000187:drug effects*; D004192:Discrimination, Psychological / Q000187:drug effects; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D004334:Drug Administration Schedule; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008694:Methamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D005082:Physical Exertion / Q000187:drug effects*; D011869:Radioligand Assay / Q000379:methods / Q000523:psychology; D051381:Rats; D020318:Rats, Long-Evans; D012201:Reward; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D008694:Methamphetamine; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D003042:Cocaine