The role of the nucleus accumbens in learned approach behavior diminishes with training

Eur J Neurosci. 2019 Nov;50(9):3403-3415. doi: 10.1111/ejn.14523. Epub 2019 Aug 19.

Abstract

Nucleus accumbens dopamine plays a key role in reward-directed approach. Past findings suggest that dopamine's role in the expression of learned behavior diminishes with extended training. However, little is known about the central substrates that mediate the shift to dopamine-independent reward approach. In the present study, rats approached and inserted the head into a reward compartment in response to a cue signaling food delivery. On days 4 and 5 of 28-trial-per-day sessions, D1 receptor antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390) infused to the NAc core reduced the probability and speed of cued approach. The disruptive effect of D1 receptor blockade was specific to the nucleus accumbens core and not seen with drug infusions to nearby dopamine target regions. In rats that received drug infusions after extended training (days 10 or 11), accumbens core D1 receptor blockade produced little effect on the expression of the same behavior. These results could have been due to a continued accumbens mediation of cued approach even after the behavior had become independent of accumbens D1 receptors. However, accumbens core ionotropic glutamate receptor blockade disrupted cued approach during early but not late stages of training, similar to the effects of D1 antagonist infusions. The results suggest that with extended training, a nucleus accumbens D1-dependent behavior becomes less dependent not only on nucleus accumbens D1 transmission but also on excitatory transmission in the nucleus accumbens. These findings fill an important gap in a growing literature on reorganization of striatal function over the course of training.

Keywords: D1 receptor; core; dopamine; expression; pavlovian; ventral striatum.

Publication types

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

MeSH terms

  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / pharmacology
  • 2-Amino-5-phosphonovalerate / administration & dosage
  • 2-Amino-5-phosphonovalerate / pharmacology
  • 6-Cyano-7-nitroquinoxaline-2,3-dione / administration & dosage
  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Animals
  • Benzazepines / administration & dosage
  • Benzazepines / pharmacology
  • Choice Behavior / drug effects
  • Choice Behavior / physiology*
  • Dopamine / metabolism
  • Dopamine / physiology*
  • Learning / drug effects
  • Learning / physiology*
  • Male
  • Microinjections
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / physiology*
  • Quinpirole / pharmacology
  • Rats
  • Reward
  • Time Factors

Substances

  • Benzazepines
  • SCH 23390
  • Quinpirole
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • 2-Amino-5-phosphonovalerate
  • Dopamine