Variations in cocaine self-administration by inbred rat strains under a progressive-ratio schedule

Area of Science:

• Neuroscience
• Behavioral Pharmacology
• Genetics

Background:

• Genetic diversity influences behavioral responses to drugs of abuse.
• Dopamine receptor genetics are implicated in drug-seeking behaviors.
• Progressive-ratio schedules reveal the reinforcing efficacy of drugs.

Purpose of the Study:

• To investigate the impact of genetic background on cocaine self-administration under a progressive-ratio schedule.
• To determine if different rat strains exhibit varying levels of cocaine reinforcement.
• To examine the differential effects of dopamine receptor antagonists on cocaine reinforcement across genetically distinct rat strains.

Main Methods:

• Utilized Fischer 344, ACI, and Brown Norway rats, known for genetic divergence.
• Assessed acquisition and stability of cocaine self-administration.
• Determined dose-effect curves for cocaine under a progressive-ratio schedule.
• Administered D1 and D2/D3 dopamine receptor antagonists to assess their impact on cocaine reinforcement.

Main Results:

• Fischer 344 rats exhibited a higher average breaking point for cocaine compared to ACI and Brown Norway rats.
• Dopamine receptor antagonists differentially affected cocaine self-administration across strains.
• The D1 antagonist SCH 23390 and D2/D3 antagonist eticlopride were more effective in reducing cocaine self-administration in Brown Norway rats.

Conclusions:

• Genetic variations significantly influence the extent of cocaine intake and reinforcement.
• Differences in dopamine receptor function across strains may underlie the observed genetic effects on cocaine reinforcement.
• These findings highlight the importance of genetic background in understanding individual differences in drug addiction vulnerability.