Age-dependent effects of chronic amphetamine on prelimbic-nucleus accumbens circuit function and goal-directed behavior

Kang, Shuo

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https://hdl.handle.net/2142/102915 Copy

Description

Title

Age-dependent effects of chronic amphetamine on prelimbic-nucleus accumbens circuit function and goal-directed behavior

Author(s)

Kang, Shuo

Issue Date

2018-12-05

Director of Research (if dissertation) or Advisor (if thesis)

Gulley, Joshua M.

Doctoral Committee Chair(s)

Gulley, Joshua M.

Committee Member(s)

• Juraska, Janice M.
• Chung, Hee Jung
• Christian, Catherine A.
• Liang, Nu-Chu

Department of Study

Neuroscience Program

Discipline

Neuroscience

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• Adolescence
• amphetamine
• prefrontal cortex
• plasticity

Language

en

Abstract

Non-medial amphetamine (AMPH) use is prevalent in the adolescent population. Empirical evidence suggests that individuals starting using drugs during adolescence have a higher chance of developing drug-related problems. It is hypothesized that adolescents may have a heightened vulnerability to drug induced plasticity such as cognitive deficits and neuroadaptations. My pilot studies suggested that the high frequency stimulation (HFS)-induced long-term depression (LTD) in the prelimbic cortex (PL) is likely to be a target influenced by repeated AMPH in an age-of-exposure dependent manner, which results in abnormalities in the reward circuit function and goal-directed behavior. Using a rat model, this hypothesis was tested with three specific aims: (1) to investigate the ontogeny of this LTD function (Experiment 1), (2) to assess the effect of adolescent and adult amphetamine on HFS-induced LTD in the PL and the potential mechanisms underlying AMPH-induced changes (Experiment 2) and (3) to determine whether AMPH-induced changes in the PL and in the reward circuit are associated with impaired cognitive flexibility (Experiment 3). In Experiment 1, field potentials in brain slices from male naive rats were assessed to test the effect of age on the expression of this LTD. The role of GABA and dopamine receptors in the HFS-induced LTD was investigated using respective agonist or antagonist. In Experiment 2, brain slices from male rats pre-exposed to repeated 3.0 mg/kg AMPH i.p injections were used in field potential and patch-clamp recordings to assess AMPH’s effect on the expression of LTD and dopamine’s modulation of inhibition. In Experiment 3, male and female rats were treated as in Experiment 2 and subjected to a strategy set-shifting task to assess AMPH’s effect on cognitive flexibility. Upon finishing the behavioral testing, each rat was sacrificed for slice recordings to assess AMPH’s effect on HFS-induced plasticity in the PL-nucleus accumbens circuit. These studies revealed unique behavioral changes and neuroadaptations following adolescent AMPH exposure. Our results are consistent with the hypothesis that adolescent brain is more vulnerable to the detrimental effect of drugs.

Graduation Semester

2018-12

Type of Resource

text

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http://hdl.handle.net/2142/102915

Copyright and License Information

Copyright 2018 Shuo Kang

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