Activating Corticotropin-Releasing Factor Systems in the Nucleus Accumbens, Amygdala, and Bed Nucleus of Stria Terminalis: Incentive Motivation or Aversive Motivation?

Biol Psychiatry. 2021 Jun 15;89(12):1162-1175. doi: 10.1016/j.biopsych.2021.01.007. Epub 2021 Jan 21.

Abstract

Background: Corticotropin-releasing factor (CRF) neural systems are important stress mechanisms in the central amygdala (CeA), bed nucleus of stria terminalis (BNST), nucleus accumbens (NAc), and related structures. CRF-containing neural systems are traditionally posited to generate aversive distress states that motivate overconsumption of rewards and relapse in addiction. However, CRF-containing systems may alternatively promote incentive motivation to increase reward pursuit and consumption without requiring aversive states.

Methods: We optogenetically stimulated CRF-expressing neurons in the CeA, BNST, or NAc using Crh-Cre+ rats (n = 37 female, n = 34 male) to investigate roles in incentive motivation versus aversive motivation. We paired CRF-expressing neuronal stimulations with earning sucrose rewards in two-choice and progressive ratio tasks and investigated recruitment of distributed limbic circuitry. We further assessed valence with CRF-containing neuron laser self-stimulation tasks.

Results: Channelrhodopsin excitation of CRF-containing neurons in the CeA and NAc amplified and focused incentive motivation and recruited activation of mesocorticolimbic reward circuitry. CRF systems in both the CeA and NAc supported laser self-stimulation, amplified incentive motivation for sucrose in a breakpoint test, and focused "wanting" on laser-paired sucrose over a sucrose alternative in a two-choice test. Conversely, stimulation of CRF-containing neurons in the BNST produced negative valence or aversive effects and recruited distress-related circuitry, as stimulation was avoided and suppressed motivation for sucrose.

Conclusions: CRF-containing systems in the NAc and CeA can promote reward consumption by increasing incentive motivation without involving aversion. In contrast, stimulation of CRF-containing systems in the BNST is aversive but suppresses sucrose reward pursuit and consumption rather than increase, as predicted by traditional hedonic self-medication hypotheses.

Keywords: Affective valence; Aversive motivation; Bed nucleus of stria terminalis; Central amygdala; Corticotropin-releasing factor; Incentive motivation; Nucleus accumbens; Optogenetics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Central Amygdaloid Nucleus* / metabolism
  • Corticotropin-Releasing Hormone / metabolism
  • Female
  • Male
  • Motivation
  • Nucleus Accumbens / metabolism
  • Rats
  • Septal Nuclei* / metabolism

Substances

  • Corticotropin-Releasing Hormone

Associated data

  • figshare/10.6084/m9.figshare.12762383
  • figshare/10.6084/m9.figshare.12762389.v1