Overexpression of ASIC1A in the nucleus accumbens of rats potentiates cocaine-seeking behavior

Addict Biol. 2020 Mar;25(2):e12690. doi: 10.1111/adb.12690. Epub 2018 Nov 6.

Abstract

Acid-sensing ion channels (ASICs) are abundantly expressed in the nucleus accumbens core (NAcore), a region of the mesolimbocortical system that has an established role in regulating drug-seeking behavior. Previous work shows that a single dose of cocaine reduced the AMPA-to-NMDA ratio in Asic1a-/- mice, an effect observed after withdrawal in wild-type mice, whereas ASIC1A overexpression in the NAcore of rats decreases cocaine self-administration. However, whether ASIC1A overexpression in the NAcore alters measures of drug-seeking behavior after the self-administration period is unknown. To examine this issue, the ASIC1A subunit was overexpressed in male Sprague-Dawley rats by injecting them with adeno-associated virus, targeted at the NAcore, after completion of 2 weeks of cocaine or food self-administration. After 21 days of homecage abstinence, rats underwent a cue-/context-driven drug/food-seeking test, followed by extinction training and then drug/food-primed, cued, and cued + drug/food-primed reinstatement tests. The results indicate that ASIC1A overexpression in the NAcore enhanced cue-/context-driven cocaine seeking, cocaine-primed reinstatement, and cued + cocaine-primed reinstatement but had no effect on food-seeking behavior, indicating a selective effect for ASIC1A in the processes underlying extinction and cocaine-seeking behavior.

Keywords: abstinence; incubation; reinstatement; self-administration; withdrawal.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acid Sensing Ion Channels / genetics*
  • Animals
  • Behavior, Animal / drug effects*
  • Cocaine / pharmacology*
  • Cocaine-Related Disorders / genetics*
  • Cocaine-Related Disorders / physiopathology
  • Disease Models, Animal
  • Dopamine Uptake Inhibitors / pharmacology
  • Gene Expression / genetics*
  • Male
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / physiopathology
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Acid Sensing Ion Channels
  • Asic1 protein, rat
  • Dopamine Uptake Inhibitors
  • Cocaine