# Brain Circuits of Outcome-dependent vs. Habitual Avoidance

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $370,679

## Abstract

Abstract
 During active avoidance (AA), subjects learn to emit instrumental actions that escape conditioned
threats and avoid pain. Little is known about the neural mechanisms mediating avoidance responses (ARs),
because AA research stalled in the 1970s amid heated theoretical debates, inconsistent results with crude
brain manipulations, and suggestions that Pavlovian processes were sufficient to explain ARs.
 This is unfortunate, as AA is the prototypical paradigm for studying aversively-motivated instrumental
behavior, a class of defensive learning that almost certainly contributes to both adaptive and maladaptive
active coping strategies. AA has several advantages as an adaptive coping/resilience mechanism: 1) it blunts
fear and anxiety reactions, 2) it is less context-dependent and more persistent than fear extinction, and, unlike
passive avoidance, 3) it allows subjects to remain engaged in environments that include danger. Conversely,
maladaptive ARs may be particularly problematic because AA is extremely resistant to extinction and
occasionally, paradoxically, enhanced by punishment (“vicious circle behavior”); processes that may be
operating in human disorders ranging from anxiety (i.e. OCD) to addiction.
 Since AA likely reflects instrumental learning layered over previously acquired fear conditioning, the
experiments in this proposal will leverage knowledge about Pavlovian fear and appetitive instrumental brain
circuits to determine training conditions and neural mechanisms mediating cognitive vs. reflexive avoidance.
Shuttlebox avoidance and a novel outcome-devaluation procedure will be used to examine the development of
AA habits in rats. Experiments will focus on resolving conflicting predictions of our “amygdala disengagement”
model of habitual AA, derived from AA studies, and the “parallel pathways” model of habit formation, derived
from studies of positive reinforcement with drugs or food. Based on converging lines of preliminary data, we
hypothesize that asymptotic ARs transition from goal-directed to habitual with time, as basolateral amygdala
(BLA) disengages and competition between parallel circuits in dorsal striatum shifts to favor stimulus-response
(S-R) over response-outcome (R-O) control. Explicit feedback cues will be included during AA training, and
outcome-devaluation will be achieved by counterconditioning (pairing response-produced safety signals with
shock). Our objectives are to determine 1) whether training- or time-dependent processes lead to habitual AA,
2) whether BLA projections to dorsomedial striatum mediate outcome-dependent AA, and 3) whether
dorsolateral striatum (DLS) mediates habitual ARs independent of central amygdala. Chemogenetic
suppression of neural activity in specific amygdalostriatal pathways will be used with devaluation to probe
avoidance circuits. If successful, these studies will demonstrate that avoidance habits depend on a time-
dependent disengagement of BLA and a shift towards DLS contr...

## Key facts

- **NIH application ID:** 9962499
- **Project number:** 5R01MH114931-04
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Christopher Kenneth Cain
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $370,679
- **Award type:** 5
- **Project period:** 2017-09-15 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9962499

## Citation

> US National Institutes of Health, RePORTER application 9962499, Brain Circuits of Outcome-dependent vs. Habitual Avoidance (5R01MH114931-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9962499. Licensed CC0.

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