Biology subjects

Fragale, J. E.

Publications and source records attributed to Fragale, J. E..

2 recordsLinked to original sources

bioRxiv2019

The Role of Orexin-1 Receptor Signaling in Demand for the Opioid Fentanyl

The orexin system is a potential treatment target for drug addiction. Orexin-1 receptor (OxR1) antagonism reduces demand for cocaine and remifentanil indicating that orexin-based therapies may reduce demand for many classes of abused drugs. However, pharmacokinetics vary greatly among opioids and it is unclear if OxR1 antagonism would reduce demand for all opioids, particularly ones with particularly high abuse liability. Here, we establish a behavioral economics (BE) procedure to assess the effects of OxR1 antagonism on demand for the highly abused opioid fentanyl. We also investigate the utility of our novel procedure in predicting OxR1 antagonism efficacy and relapse propensity. The OxR1 antagonist SB-334867 (SB) increased demand elasticity (; decreased motivation) for fentanyl without affecting preferred consumption of fentanyl at null cost (Qo). Baseline values predicted SB efficacy, such that SB was most effective at increasing demand elasticity in highly motivated rats. SB also attenuated cue-induced fentanyl seeking and baseline values predicted the amount of reinstatement behavior. These results highlight the promise of the orexin system as a treatment target for opioid addiction and emphasize the usefulness of BE procedures in the study of opioid abuse.

animal behavior and cognition↗

bioRxiv2019

Anhedonia following mild traumatic brain injury in rats: A behavioral economic analysis of positive and negative reinforcement

Psychiatric disorders affect nearly 50% of individuals who have experienced a traumatic brain injury (TBI). Anhedonia is a major symptom of numerous psychiatric disorders and is a diagnostic criterion for depression. Recently, anhedonia has been divided into consummatory, motivational and decisional components, all of which may be affected differently in disease. Although anhedonia is typically assessed using positive reinforcement, the importance of stress in psychopathology suggests the study of negative reinforcement (removal or avoidance of aversive events) may be equally important. The present study investigated positive and negative reinforcement following a rat model of mild TBI (mTBI) using lateral fluid percussion. Hedonic value of and motivation for reinforcement was determined by behavioral economic analyses. Following mTBI, the hedonic value of avoiding foot shock was reduced. In contrast, the hedonic value of escaping foot shock or obtaining a sucrose pellet was not altered by mTBI. Moreover, neither motivation to avoid or escape foot shock nor motivation to acquire sucrose was modified by mTBI. Our results suggest that individuals experiencing mTBI may experience more stress because of poor proactive control of stress resulting from reduced hedonic value of avoiding aversive events.

animal behavior and cognition↗