Effects of Acute Sleep Deprivation in the Reinstatement of Fentanyl Self-Administration in Male and Female Rats: Evaluation of the Opioidergic Pathway Modulation

• Grant number: 24/15513-8
• Support Opportunities: Scholarships in Brazil - Master
• Start date: December 01, 2024
• End date: September 30, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Fabio Cardoso Cruz
• Grantee: Victor Nascimento Rocha
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 18/15505-4 - Neurobiology study of relapse to alcohol and cocaine seeking: identification of plasticity in neuronal ensembles that encodes addiction-related memories, AP.JP2

Abstract

Opioid Use Disorder (OUD) is associated with the chronic consumption of these substances, among which fentanyl stands out as being responsible for the highest number of overdose-related deaths worldwide. This condition is established through a conjunction of biopsychosocial factors, and its treatment presents several challenges. Among these, stress plays a crucial role in increasing patients' vulnerability to relapse. Various factors can contribute to stress in these patients, including insomnia and disrupted sleep architecture-symptoms that may even stem from opioid use itself, creating a cyclical relationship. However, the neurobiology of sleep as a stress-inducing factor that promotes relapse is not well understood, nor is its relationship with changes in the expression of opioid receptors and endogenous peptides. In animals, relapse can be studied using the operant self-administration model, and sleep disruption can be induced through total or partial deprivation, as sleep consists of stages characterized by different neural wave patterns. Therefore, in the present study, we propose to investigate the effects of impairing different sleep stages on the reinstatement of fentanyl-seeking behavior in rats to evaluate: i) the influence of total sleep deprivation or slow-wave sleep deprivation, using the Gentle Handling and Multiple Platforms techniques, respectively, on fentanyl relapse; ii) potential sex differences in the response to sleep deprivation and subsequent fentanyl-seeking reinstatement; iii) plasma corticosterone levels in animals subjected to sleep deprivation protocols; iv) potential changes in the expression of opioid receptors and related endogenous peptides during sleep-deprivation-induced fentanyl-seeking reinstatement; and v) the effects of specific and non-specific opioid antagonists on sleep-deprivation-induced fentanyl relapse.