Non-invasive self administration methodology for mice

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DESCRIPTION (provided by applicant): Abuse of addictive drugs puts an enormous burden on society, yet many basic questions regarding drug craving pathways remain poorly understood. Current animal models of drug-self-administration are limited by technical difficulties associated with the invasive procedures required for small animals, particularly in the genetically tractable mouse. Here we describe the development of a non-invasive procedure for drug self-administration that is particularly suited for use in mouse. Preliminary studies conducted in the laboratory of Dr. David Stephens have shown that mice can be trained to self-administer an aqueous solution of cocaine delivered intranasally via an aerosol spray. Here we propose to replicate these results and further develop and apply these methods. Specific aims include: 1. Replication of the initial data generated in Stephens' laboratory, using newly constructed behavioral apparati in our own laboratory. 2. Controls to further validate the self-administration paradigm: these controls include use of related but nonaddicting substances such as lidocaine and measurement of additional physiological correlates of cocaine exposure. The measurements will include determination of serum and brain cocaine levels, and measurement of locomotor and heart-rate stimulation following cocaine exposure. 3. Application of this paradigm to mouse circadian mutants. These studies are based on the observation that mper 1 knockout mice show a lack of conditioned place preference to cocaine. We will study these mice as well as mper 1 and 3 knockouts, and mutants in several other circadian genes. These studies should address the question of whether the defect is specific to cocaine versus defects in more general reward pathways. 4. Screen candidate animals from the Neuromice.org recessive behavioral screen that show alterations in intitial cocaine responses. Initial screening for cocaine responsiveness is showing a large number of 'putants', 36 as of this writing. These mice will be made available to the scientific community even before they are fully characterized. We will obtain these lines when available as homozygotes and test them in our paradigm.