Aversion-resistant fentanyl self-administration in mice
- PDF / 1,511,157 Bytes
- 12 Pages / 595.276 x 790.866 pts Page_size
- 67 Downloads / 188 Views
ORIGINAL INVESTIGATION
Aversion-resistant fentanyl self-administration in mice Sean C. Monroe 1 & Anna K. Radke 1 Received: 8 June 2020 / Accepted: 13 November 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Rationale Animal models of compulsive drug use that continues despite negative consequences can be used to investigate the neural mechanisms of addiction. However, models of punished or aversion-resistant opioid self-administration are notably lacking. Objectives We sought to develop an aversion-resistant, oral fentanyl self-administration paradigm. Methods In Experiment 1, C57BL/6J male and female, adult mice consumed fentanyl (10 μg/mL) in a two-bottle drinking in the dark task and escalating concentrations of quinine were added to the bottles. In Experiment 2, mice were trained to administer oral fentanyl (10 μg/mL) in an operant response task. Quinine was next added to the fentanyl solution in escalating concentrations. In Experiment 3, mice were trained to respond for oral fentanyl or fentanyl adulterated with 500 μM quinine on every session. In Experiment 4, mice were trained to respond for a 1% sucrose solution before introduction of quinine. Results Quinine reduced two-bottle choice consumption in males but not in females. Both sexes demonstrated the ability to detect the selected concentrations of quinine in fentanyl. In the operant chamber, mice responded robustly for oral fentanyl but introduction of quinine at any stage of training was insufficient to reduce responding. In contrast, quinine reduced responding for sucrose at concentrations above 250 μM. Conclusions Mice will respond for and consume oral fentanyl in both a two-bottle choice and an operant response task. Quinine is detectable in fentanyl but mice will continue to respond for and consume fentanyl with quinine in both paradigms. These data support the use of these models in behavioral studies of compulsive-like opioid use. Keywords Addiction . Opioid . Mouse . Compulsive . Quinine
Introduction Drug addiction is characterized by uncontrollable drug use that persists in the face of serious negative consequences (i.e., compulsiveness) (Everitt and Robbins 2005). This presents a major challenge to those suffering from addiction and is thought to involve aberrant activity in brain reward systems (Kenny 2007). Despite the fact that addiction is a significant problem that affects millions of individuals worldwide, treatments are limited in both the options available as well as their effectiveness (Veilleux et al. 2010; Peacock et al. 2018). As such, preclinical animal research investigating the neural mechanisms behind this problem is critically needed to
* Anna K. Radke [email protected] 1
Department of Psychology and Center for Neuroscience and Behavior, Miami University, 90 N Patterson Ave, Oxford, OH 45056, USA
advance treatment options and to understand the biology of this disease. In the United States, rates of illicit opioid use and overdose have skyrocketed in recent years. This problem has overwhelmed
Data Loading...
