# Neural mechanisms preventing postpartum relapse to cocaine seeking in new mothers

> **NIH NIH R21** · UNIVERSITY OF MASSACHUSETTS AMHERST · 2022 · $234,795

## Abstract

Project Summary
Relapse to cocaine use in postpartum women is a serious health problem that impacts the mother’s ability to
care for her child, with life-long consequences for both the mother and child. There is a window of opportunity
for treatment in the early postpartum period, as cocaine use in new mothers is significantly reduced by the
competing motivation related to child rearing. Unfortunately, few women maintain abstinence and relapse to
cocaine use beyond the first 6 months following their child’s birth. To date, little is known regarding the
neurobiological mechanisms by which maternal motivation can prevent relapse to cocaine seeking in new
mothers. The current proposal builds logically on my work from the past several years. Our prior work in rats
demonstrates that during the unique early postpartum period, new mothers also reduce cocaine seeking, and
that pharmacological inactivation of the medial preoptic area (mPOA), a critical structure orchestrating maternal
behavior, results in increased maternal choice of cocaine-conditioned incentives in a concurrent pup/cocaine
choice conditioned place preference (CPP) task. The objective of this proposal is to delineate the neural
processes underlying the transient resistance to cocaine relapse in new mothers. To accomplish this goal, we
will use a novel adaptation of the extinction-reinstatement CPP animal model of drug relapse and a pathway-
specific chemogenetic approach to determine the role of mPOA neurons projecting to the infralimbic cortex (IL)
and the ventral tegmental area (VTA) in preventing reinstatement of cocaine seeking in abstinent new mother
rats. Both structures receive direct input from the mPOA and are critical nodes of the circuitry that mediates
reward and response allocation, with the IL contributing to stimulus recognition and executive functions, and the
VTA modulating the behavioral strategy via dopamine projections to the nucleus accumbens. The experiments
in AIM 1 will use combined injections of a Cre-dependent inhibitory (hM4Di) or excitatory (hM3Dq) designer
receptors exclusively activated by designer drugs (DREADD) AAV into the mPOA, with a retrograde transducing
CAV2-Cre virus into the IL to assess the functional necessity and sufficiency of the mPOA à IL pathway on
reinstatement of cocaine seeking in new mothers. Experiments in AIM 2 will determine the role of monosynaptic
mPOA projections to the VTA (mPOAàVTA) in preventing reinstatement of previously extinguished cocaine
seeking behavior in new mothers. This AIM will also use Gi- or Gq-DREADDs combined with CAV2-Cre to
selectively manipulate mPOAàVTA pathway during reinstatement of cocaine CPP. The impact of these
mPOAàIL and mPOAàVTA chemogenetic manipulations on maternal behavior will be also studied.
Considering the consequences of maternal cocaine use on both mother and child health, it is of major clinical
significance to understand the neurobiology contributing to this relapse-resistant state. This p...

## Key facts

- **NIH application ID:** 10354553
- **Project number:** 1R21DA055169-01
- **Recipient organization:** UNIVERSITY OF MASSACHUSETTS AMHERST
- **Principal Investigator:** Mariana Pereira Arboleya
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $234,795
- **Award type:** 1
- **Project period:** 2022-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10354553

## Citation

> US National Institutes of Health, RePORTER application 10354553, Neural mechanisms preventing postpartum relapse to cocaine seeking in new mothers (1R21DA055169-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10354553. Licensed CC0.

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