Morales, Danna (2025) Involvement of Corticotropin-Releasing Factor Signaling in Food Deprivation Stress-Induced Heroin Seeking Following Punishment-Imposed Abstinence in Male Rats. Masters thesis, Concordia University.
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Abstract
Relapse remains a major challenge in treating opioid use disorder, often triggered by
stress-related factors that reinstate drug-seeking after abstinence. Corticotropin-releasing factor (CRF), a neuropeptide central to the stress response, has been implicated in stress-induced relapse, particularly via the mesolimbic dopamine system. However, the neural sources of relapse-driving CRF remain unclear. This thesis investigates CRF signaling in stress-induced heroin seeking and examines the paraventricular nucleus of the hypothalamus (PVN), a CRF expressing region, as a potential driver.
In the first experiment, male rats were trained to self-administer heroin using a seek-take chain schedule modeling human drug use. After stable intake, rats underwent punishment-imposed abstinence, where footshocks were probabilistically paired with drug-seeking responses, leading to suppression. During relapse testing, each rat was evaluated under two conditions: sated and food deprived. Heroin-seeking behavior was significantly higher under food deprivation than when sated. This increase was blocked by intracerebroventricular administration of a CRF receptor antagonist, supporting CRF’s role in stress-induced relapse and validating the seek-take punishment model.
In the second experiment, the PVN was targeted to explore its contribution to relapse.
Rats underwent the same protocol and received either a ligand to chemogenetically inhibit PVN neurons or vehicle before relapse testing. PVN inhibition modestly reduced heroin seeking under food deprivation but did not reach strong statistical certainty. These results suggest the PVN may contribute to CRF-driven relapse, though further studies are needed.
Together, these findings highlight CRF’s role in stress-induced relapse and suggest involvement of multiple CRF-releasing regions.
| Divisions: | Concordia University > Research Units > Centre for Studies in Behavioural Neurobiology |
|---|---|
| Item Type: | Thesis (Masters) |
| Authors: | Morales, Danna |
| Institution: | Concordia University |
| Degree Name: | M.A. |
| Program: | Psychology |
| Date: | 25 July 2025 |
| Thesis Supervisor(s): | Shalev, Uri |
| Keywords: | Corticotropin-Releasing Factor, Substance Use Disorder, Stress-Induced Relapse, Punishment-Imposed Abstinence, Paraventricular Nucleus of the Hypothalamus |
| ID Code: | 996038 |
| Deposited By: | Danna Itzel Morales Velarde |
| Deposited On: | 04 Nov 2025 17:28 |
| Last Modified: | 04 Nov 2025 17:28 |
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