PhD Oral Exam - Catarina Borges, Psychology

When studying for a doctoral degree (PhD), candidates submit a thesis that provides a critical review of the current state of knowledge of the thesis subject as well as the student’s own contributions to the subject. The distinguishing criterion of doctoral graduate research is a significant and original contribution to knowledge.

Once accepted, the candidate presents the thesis orally. This oral exam is open to the public.

Abstract

This dissertation introduces and validates a novel stress-induced relapse model: acute food deprivation–induced heroin seeking following punishment-imposed abstinence. Behaviourally, acute food deprivation robustly reinstated heroin seeking in male and female rats, even after prolonged abstinence, while cue- or food-deprivation-induced craving showed no incubation, consistent with voluntary abstinence models. To our knowledge, this is the first study to examine stress-induced heroin relapse after punishment-imposed abstinence and to investigate incubation of stress-induced cravings under these conditions.

Neurobiological investigations identify the posterior paraventricular nucleus of the thalamus (pPVT) as a critical mediator of food-deprivation stress–induced relapse. Chemogenetic inhibition of the pPVT significantly increased heroin seeking under food deprivation, and unexpectedly, activation produced a similar effect, suggesting a complex modulatory role rather than a simple “on-off” mechanism. Previous studies suggest that 24 hours of food deprivation inhibits pPVT activity through hypothalamic GABAergic inputs (AgRP, LHA, zona incerta), which may disinhibit heroin-seeking behaviour through downstream circuits involving NAcShell PV interneurons and D2/D1 medium spiny neurons (MSNs). We propose that pPVT inhibition reduces activity in PV and D2 MSNs, thereby disinhibiting D1 MSNs and promoting heroin seeking under motivational conflict.

Additional regions, including the infralimbic cortex, BNST, and BLA, may contribute independently, reflecting the interplay between stress, reward, and conflict processing. These findings position the pPVT within a thalamo-striatal network integrating stress and motivational signals, highlighting caloric stress as a clinically relevant relapse trigger and underscoring the need for cell-specific investigations to inform targeted interventions.