title: Repeated exposure to amphetamine during adolescence alters inhibitory tone in the medial prefrontal cortex following drug re-exposure in adulthood.
abstract: Behavioral sensitization following repeated amphetamine (AMPH) exposure is associated with changes in GABA function in the medial prefrontal cortex (mPFC). In rats exposed to AMPH during adolescence compared to adulthood, there are unique patterns of sensitization that may reflect age-dependent differences in drug effects on prefrontal GABAergic function. In the current study, we used a sensitizing regimen of repeated AMPH exposure in adolescent and adult rats to determine if a post-withdrawal AMPH challenge would alter inhibitory transmission in the mPFC in a manner that depends on age of exposure. Male Sprague-Dawley rats were treated with saline or 3mg/kg AMPH (i.p.) during adolescence [postnatal day (P) 27-P45] or adulthood (P85- P103) and were sacrificed either at similar ages in adulthood (∼P133; experiment 1) or after similar withdrawal times (3-4 weeks; experiment 2). Spontaneous inhibitory postsynaptic currents (sIPSCs) were recorded in vitro from deep layer pyramidal cells in the mPFC using the whole-cell configuration. We found no effect of AMPH pre-exposure on baseline sIPSC frequency. Subsequent application of AMPH (25μM) produced a stable increase in sIPSC frequency in controls, suggesting that AMPH increases inhibitory tone in the mPFC. However, AMPH failed to increase sIPSCs in adolescent- or adult-exposed rats. In experiment 2, where withdrawal period was kept similar for both exposure groups, AMPH induced a suppression of sIPSC activity in adolescent-exposed rats. These results suggest that sensitizing treatment with AMPH during adolescence or adulthood dampens inhibitory influences on mPFC pyramidal cells, but potentially through different mechanisms.
authors.affiliation: Neuroscience Program, University of Illinois, Urbana-Champaign.|Department of Molecular and Integrative Physiology, University of Illinois, Urbana-Champaign.|Beckman Institute for Advanced Science, University of Illinois, Urbana-Champaign.
authors.forename: Kush
authors.initials: K
authors.lastname: Paul
authors.affiliation: Neuroscience Program, University of Illinois, Urbana-Champaign.
authors.forename: Shuo
authors.initials: S
authors.lastname: Kang
authors.affiliation: Neuroscience Program, University of Illinois, Urbana-Champaign.|Department of Molecular and Integrative Physiology, University of Illinois, Urbana-Champaign.|Department of Pharmacology, University of Illinois, Urbana-Champaign.|Beckman Institute for Advanced Science, University of Illinois, Urbana-Champaign.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Cox
authors.affiliation: Neuroscience Program, University of Illinois, Urbana-Champaign.|Department of Psychology, University of Illinois, Urbana-Champaign.|Institute for Genomic Biology, University of Illinois, Urbana-Champaign.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Gulley
mesh_terms: D000661:Amphetamine / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D008297:Male; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000254:growth & development* / Q000503:physiopathology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D017207:Rats, Sprague-Dawley; D046509:Tissue Culture Techniques
chemical_list: D000697:Central Nervous System Stimulants; D000661:Amphetamine
keywords: Adolescence; Amphetamine; GABA; Medial prefrontal cortex; Whole-cell recording