title: Sex differences, learning flexibility, and striatal dopamine D1 and D2 following adolescent drug exposure in rats.
abstract: Corticostriatal circuitry supports flexible reward learning and emotional behavior from the critical neurodevelopmental stage of adolescence through adulthood. It is still poorly understood how prescription drug exposure in adolescence may impact these outcomes in the long-term. We studied adolescent methylphenidate (MPH) and fluoxetine (FLX) exposure in rats and their impact on learning and emotion in adulthood. In Experiment 1, male and female rats were administered MPH, FLX, or saline (SAL), and compared with methamphetamine (mAMPH) treatment beginning in postnatal day (PND) 37. The rats were then tested on discrimination and reversal learning in adulthood. In Experiment 2, animals were administered MPH or SAL also beginning in PND 37 and later tested in adulthood for anxiety levels. In Experiment 3, we analyzed striatal dopamine D1 and D2 receptor expression in adulthood following either extensive learning (after Experiment 1) or more brief emotional measures (after Experiment 2). We found sex differences in discrimination learning and attenuated reversal learning after MPH and only sex differences in adulthood anxiety. In learners, there was enhanced striatal D1, but not D2, after either adolescent MPH or mAMPH. Lastly, also in learners, there was a sex x treatment group interaction for D2, but not D1, driven by the MPH-pretreated females, who expressed significantly higher D2 levels compared to SAL. These results show enduring effects of adolescent MPH on reversal learning in rats. Developmental psychostimulant exposure may interact with learning to enhance D1 expression in adulthood, and affect D2 expression in a sex-dependent manner.
authors.affiliation: Department of Psychology, The Brain Research Institute, University of California at Los Angeles, Los Angeles, CA, USA; Integrative Center for Addictions, University of California at Los Angeles, Los Angeles, CA, USA; Integrative Center for Learning and Memory, University of California at Los Angeles, Los Angeles, CA, USA. Electronic address: aizquie@psych.ucla.edu.
authors.forename: Alicia
authors.initials: A
authors.lastname: Izquierdo
authors.affiliation: Department of Psychology, The Brain Research Institute, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Hilda
authors.initials: H
authors.lastname: Pozos
authors.affiliation: Department of Psychology, The Brain Research Institute, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Adrianna De La
authors.initials: Ade L
authors.lastname: Torre
authors.affiliation: Department of Psychology, The Brain Research Institute, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Simone
authors.initials: S
authors.lastname: DeShields
authors.affiliation: Department of Psychology, The Brain Research Institute, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: James
authors.initials: J
authors.lastname: Cevallos
authors.affiliation: Department of Psychology, The Brain Research Institute, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rodriguez
authors.affiliation: Department of Psychology, The Brain Research Institute, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Stolyarova
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D007858:Learning / Q000187:drug effects*; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D008774:Methylphenidate / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D012727:Sex Characteristics
chemical_list: D000697:Central Nervous System Stimulants; D018765:Dopamine Uptake Inhibitors; D005473:Fluoxetine; D008694:Methamphetamine; D008774:Methylphenidate; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Anxiety; Dopamine receptors; Psychostimulants; Reversal learning; Sex; Striatum