title: Adolescent exposure to cocaine, amphetamine, and methylphenidate cross-sensitizes adults to methamphetamine with drug- and sex-specific effects.
abstract: The increasing availability, over-prescription, and misuse and abuse of ADHD psychostimulant medications in adolescent populations necessitates studies investigating the long-term effects of these drugs persisting into adulthood. Male and female C57Bl/6J mice were exposed to amphetamine (AMPH) (1.0 and 10 mg/kg), methylphenidate (MPD) (1.0 and 10 mg/kg), or cocaine (COC) (5.0 mg/kg) from postnatal day 22 to 31, which represents an early adolescent period. After an extended period of drug abstinence, adult mice were challenged with a subacute methamphetamine (METH) dose (0.5 mg/kg), to test the long-term effects of adolescent drug exposures on behavioral cross-sensitization using an open field chamber. There were no sex- or dose-specific effects on motor activity in adolescent, saline-treated controls. However, AMPH, MPD, and COC adolescent exposures induced cross-sensitization to a subacute METH dose in adulthood, which is a hallmark of addiction and a marker of long-lasting plastic changes in the brain. Of additional clinical importance, AMPH-exposed male mice demonstrated increased cross-sensitization to METH in contrast to the female-specific response observed in MPD-treated animals. There were no sex-specific effects after adolescent COC exposures. This study demonstrates differential drug, dose, and sex-specific alterations induced by early adolescent psychostimulant exposure, which leads to behavioral alterations that persist into adulthood.
authors.affiliation: Department of Biology, University of North Georgia, Dahlonega, GA, USA. Electronic address: ryan.shanks@ung.edu.
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Shanks
authors.affiliation: Department of Psychological Science, University of North Georgia, Dahlonega, GA, USA. Electronic address: jross34@uthsc.edu.
authors.forename: Jordan M
authors.initials: JM
authors.lastname: Ross
authors.affiliation: Department of Psychological Science, University of North Georgia, Dahlonega, GA, USA. Electronic address: hdoyle2@student.gsu.edu.
authors.forename: Hillary H
authors.initials: HH
authors.lastname: Doyle
authors.affiliation: Department of Biology, University of North Georgia, Dahlonega, GA, USA. Electronic address: ahelton17@lawmail.mercer.edu.
authors.forename: Amanda K
authors.initials: AK
authors.lastname: Helton
authors.affiliation: Department of Psychological Science, University of North Georgia, Dahlonega, GA, USA. Electronic address: bnwhit0903@gmail.com.
authors.forename: Brittany N
authors.initials: BN
authors.lastname: Picou
authors.affiliation: Department of Psychological Science, University of North Georgia, Dahlonega, GA, USA. Electronic address: jaschu0810@ung.edu.
authors.forename: Jordyn
authors.initials: J
authors.lastname: Schulz
authors.affiliation: Department of Psychological Science, University of North Georgia, Dahlonega, GA, USA. Electronic address: cmtava5928@ung.edu.
authors.forename: Chris
authors.initials: C
authors.lastname: Tavares
authors.affiliation: Department of Biology, University of North Georgia, Dahlonega, GA, USA. Electronic address: sabrya8328@ung.edu.
authors.forename: Sarah
authors.initials: S
authors.lastname: Bryant
authors.affiliation: Department of Psychological Science, University of North Georgia, Dahlonega, GA, USA. Electronic address: bryan.dawson@ung.edu.
authors.forename: Bryan L
authors.initials: BL
authors.lastname: Dawson
authors.affiliation: Department of Psychological Science, University of North Georgia, Dahlonega, GA, USA. Electronic address: steven.lloyd@ung.edu.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Lloyd
mesh_terms: D000375:Aging / Q000523:psychology; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007274:Injections, Intraperitoneal; D008124:Locomotion / Q000187:drug effects; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D008774:Methylphenidate / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D012737:Sex Factors; D013997:Time Factors
chemical_list: D000697:Central Nervous System Stimulants; D008774:Methylphenidate; D008694:Methamphetamine; D000661:Amphetamine; D003042:Cocaine
keywords: Addiction; Adolescence; Cross-sensitization; Mice; Psychostimulants; Sex-specific effects