Cocaine self-administration is complexly determined trait, and a substantial proportion of individual differences in cocaine use is determined by genetic variation. Cocaine intravenous self-administration (IVSA) procedures in laboratory animals provide opportunities to prospectively investigate neurogenetic influences on the acquisition of voluntary cocaine use. Large and genetically diverse mouse populations, like the Hybrid Mouse Diversity Panel (HMDP), have been developed for forward genetic approaches that can reveal genetic variants that influence traits like cocaine IVSA. This population enables high resolution and well-powered genome wide association studies, as well as the discovery of genetic correlations. Here, we provide information on cocaine (or saline - as a control) IVSA in 65 strains of the HMDP. We found cocaine IVSA to be substantially heritable in this population, with strain-level intake ranging for near zero to >25 mg/kg/session. Though saline IVSA was also found to be heritable, a very modest genetic correlation between cocaine and saline IVSA indicates that operant responding for the cocaine reinforcer was influenced by a substantial proportion of unique genetic variants. These data indicate that the HMDP is suitable for forward genetic approaches for the analysis of cocaine IVSA, and this project has also led to the discovery of reference strains with extreme cocaine IVSA phenotypes, revealing them as polygenic models of risk and resilience to cocaine reinforcement. This is part of an ongoing effort to characterize genetic and genomic variation that moderates cocaine IVSA, which may, in turn, provide a more comprehensive understanding of cocaine risk genetics and neurobiology.

Measurement of drinking behavior in laboratory animals is an often utilized method in many areas of scientific research, including the study of ingestive behaviors and addictions. We have designed a system that measures drinking by continuously tracking fluid-filled bottle weights with load cells and calculating change in fluid weight per drinking bout. The load cells serve both as a contact sensor that detects mouse-spout contact, as well as a monitor of fluid weight change per contact bout. The design described here fulfills several key criteria, including automated and continuous recording of drinking in the home-cage, automated control of liquid access, and inexpensive/reproducible fabrication. These features may allow researchers to generate high-resolution, detailed information on drinking behavior in high-throughput experimental designs. Here, we provide an overview of the design and present results from tests to validate the system. C57BL/6J mice were offered water and ethanol concurrently, using this system. Consumption weights were determined by the system and independently by conventional approaches. The results indicated a near-perfect correlation between the two methods, indicating the system returned valid consumption weights. This system functions as a valid drinking monitor that provides temporally precise data with a low cost design.