title: D1 receptor-mediated inhibition of medial prefrontal cortex neurons is disrupted in adult rats exposed to amphetamine in adolescence.
abstract: Amphetamine (AMPH) exposure leads to changes in behavior and dopamine receptor function in the prefrontal cortex (PFC). Since dopamine plays an important role in regulating GABAergic transmission in the PFC, we investigated if AMPH exposure induces long-lasting changes in dopamine's ability to modulate inhibitory transmission in the PFC as well as whether the effects of AMPH differed depending on the age of exposure. Male Sprague-Dawley rats were given saline or 3 mg/kg AMPH (i.p.) repeatedly during adolescence or adulthood and following a withdrawal period of up to 5 weeks (Experiment 1) or up to 14 weeks (Experiment 2), they were sacrificed for in vitro whole-cell recordings in layer V/VI of the medial PFC. We found that in brain slices from either adolescent- or adult-exposed rats, there was an attenuation of dopamine-induced increases in inhibitory synaptic currents in pyramidal cells. These effects did not depend on age of exposure, were mediated at least partially by a reduced sensitivity of D1 receptors in AMPH-treated rats, and were associated with an enhanced behavioral response to the drug in a separate group of rats given an AMPH challenge following the longest withdrawal period. Together, these data reveal a prolonged effect of AMPH exposure on medial PFC function that persisted for up to 14 weeks in adolescent-exposed animals. These long-lasting neurophysiological changes may be a contributing mechanism to the behavioral consequences that have been observed in those with a history of amphetamine abuse.
authors.affiliation: Neuroscience Program, University of Illinois, Urbana-Champaign, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kang
authors.affiliation: Neuroscience Program, University of Illinois, Urbana-Champaign, USA; Department of Molecular and Integrative Physiology, University of Illinois, Urbana-Champaign, USA; Beckman Institute for Advanced Science, University of Illinois, Urbana-Champaign, USA.
authors.forename: K
authors.initials: K
authors.lastname: Paul
authors.affiliation: Department of Psychology, University of Illinois, Urbana-Champaign, USA.
authors.forename: E R
authors.initials: ER
authors.lastname: Hankosky
authors.affiliation: Neuroscience Program, University of Illinois, Urbana-Champaign, USA; Department of Molecular and Integrative Physiology, University of Illinois, Urbana-Champaign, USA; Department of Pharmacology, University of Illinois, Urbana-Champaign, USA; Beckman Institute for Advanced Science, University of Illinois, Urbana-Champaign, USA. Electronic address: coxclee@msu.edu.
authors.forename: C L
authors.initials: CL
authors.lastname: Cox
authors.affiliation: Neuroscience Program, University of Illinois, Urbana-Champaign, USA; Department of Psychology, University of Illinois, Urbana-Champaign, USA; Institute for Genomic Biology, University of Illinois, Urbana-Champaign, USA. Electronic address: jgulley@illinois.edu.
authors.forename: J M
authors.initials: JM
authors.lastname: Gulley
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000661:Amphetamine / Q000633:toxicity*; D019969:Amphetamine-Related Disorders / Q000378:metabolism; D000818:Animals; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D004298:Dopamine / Q000378:metabolism / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology; D013375:Substance Withdrawal Syndrome; D046509:Tissue Culture Techniques
chemical_list: D000697:Central Nervous System Stimulants; D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000661:Amphetamine; D004298:Dopamine
keywords: D(1) receptors; adolescent; amphetamine; plasticity; sIPSC; whole-cell recordings