A drug-vs-food ?choice? self-administration procedure in rats to investigate pharmacological and environmental mechanisms of substance use disorders

Background: Preclinical drug self-administration procedures are commonly used to investigate expression, mechanisms, and treatment of substance use disorders. New method: The aims were to back-translate an intravenous drug-vs-food choice procedure primarily utilized in monkeys to male and female rats and to develop a surgical method for sustained intravenous catheter patency suitable for long-term drug-choice studies. Results: The surgical protocol resulted in a median intravenous jugular catheter patency in male and female rats of 126 days (range: 25?365 days). Drug-vs-food choice was established with opioids (fentanyl and heroin), psychostimulants (cocaine, methamphetamine, and amphetamine), and an opioid/psychostimulant mixture (fentanyl + methamphetamine). The average time from catheter implantation to stable choice behavior across all drugs was 27 sessions (range: 16?44 sessions). Choice behavior stabilized more quickly for cocaine and fentanyl than for other drugs. Manipulations of both environmental variables (e.g., response requirement or food reinforcer magnitude) and pharmacological variables (e.g., extended access drug self-administration or continuous buprenorphine treatment via osmotic pump) significantly shifted opioid-vs-food choice consistent with previous monkey studies. Comparison with existing methods: Duration of intravenous catheter patency in rats was suitable for long-term, within-subject drug choice studies. Effects of environmental and pharmacological manipulations in rats confirmed and extended previous results from monkeys. Conclusions: The concordance of behavioral results between rats and monkeys using the present drug-vs-food choice procedure supports its utility to improve our basic understanding of the expression and mechanisms of substance use disorders towards to development of more effective therapeutics.

Automated summary

The study successfully transferred the intravenous drug-vs-food choice procedure from monkeys to male and female rats, and developed a surgical method suitable for long-term drug choice studies. Results showed that rats can be used to study drug choice behavior, and that choice behavior is stable in response to both environmental and pharmacological manipulations.