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Behav Brain Res. 2015 Mar 15;281:116-24. doi: 10.1016/j.bbr.2014.12.002. Epub 2014 Dec 8.

Adolescent exposure to cocaine, amphetamine, and methylphenidate cross-sensitizes adults to methamphetamine with drug- and sex-specific effects.

Author information

1
Department of Biology, University of North Georgia, Dahlonega, GA, USA. Electronic address: ryan.shanks@ung.edu.
2
Department of Psychological Science, University of North Georgia, Dahlonega, GA, USA. Electronic address: jross34@uthsc.edu.
3
Department of Psychological Science, University of North Georgia, Dahlonega, GA, USA. Electronic address: hdoyle2@student.gsu.edu.
4
Department of Biology, University of North Georgia, Dahlonega, GA, USA. Electronic address: ahelton17@lawmail.mercer.edu.
5
Department of Psychological Science, University of North Georgia, Dahlonega, GA, USA. Electronic address: bnwhit0903@gmail.com.
6
Department of Psychological Science, University of North Georgia, Dahlonega, GA, USA. Electronic address: jaschu0810@ung.edu.
7
Department of Psychological Science, University of North Georgia, Dahlonega, GA, USA. Electronic address: cmtava5928@ung.edu.
8
Department of Biology, University of North Georgia, Dahlonega, GA, USA. Electronic address: sabrya8328@ung.edu.
9
Department of Psychological Science, University of North Georgia, Dahlonega, GA, USA. Electronic address: bryan.dawson@ung.edu.
10
Department of Psychological Science, University of North Georgia, Dahlonega, GA, USA. Electronic address: steven.lloyd@ung.edu.

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.

KEYWORDS:

Addiction; Adolescence; Cross-sensitization; Mice; Psychostimulants; Sex-specific effects

PMID:
25496784
DOI:
10.1016/j.bbr.2014.12.002
[Indexed for MEDLINE]

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