Brief Report animals that did not exhibit rapid sedation were omitted from is an important component of cocaine addiction3. The IV the trials. After stable self-administration maintenance was self-administration model is thus an invaluable method for displayed, mice progressed to a dose-response schedule (Fig investigating drug-seeking behaviors. This self-administration 1c). The effects of differential doses on cocaine intake reflect the preparation uses inexpensive and durable catheter supplies that successful and efficient delivery of cocaine to the jugular vein, can be easily assembled for successful self-administration testing. and the behavioral sensitivity of the animals to the change in The advantages to this method include ease of use, affordable supplies for construction and reliable IV drug delivery. Our cocaine dose. cocaine self-administration catheter procedure serves as reliable, low-cost method that is easy to integrate into any drug laboratory environment. METHODS The construction of the self-administration apparatus begins with assembly of the animal boxes, which contain six animal housing units each equipped with two nose-poke response portals. These are built from custom cut pieces of black acrylic adhered together using strong solvent cement with clear retracting doors attached with a plastic hinge (Supplementary Methods, www. Neuro-Cloud.net/nature-precedings/pomrenze). Beam breaks at the nose-poke operandums, each of which contain an infrared photosensor and a white LED, are reinforced with a light cue and cocaine reward in the active portal and have no consequence in the inactive portal. Premade Custom mouse catheters can be obtained by visiting www.neuro-cloud.net/nature-precedings/ pomrenze and making a request. Catheters are constructed using ordinary 23 gauge needles (Precision Glide, Becton Dickinson). Needles are extracted from the plastic dispensers and the bevels are snapped off. The nozzles of the 5mL syringes are sawed off and shaved down to be smooth and contoured. The plastic needle dispensers are shaved down as needed and inserted into the syringe nozzles so that the nozzle serves as a platform for the upright standing dispenser. After a slit is made in the base of the nozzle, the needle plumbing is bent at a right angle, adhered to Silastic tubing with a reinforcing section of Tygon tubing, and forced through the dispenser. The base of the Fig 2: Catheters are constructed using 1) Hypodermic needles and dispensers nozzle is reinforced with superglue and filled with liquid latex (white) 2) Shaved 5 mL syringe nozzles (red) and 3) Silastic and Tygon to prevent any catheter leaking (Fig 2). Finalized catheters are tubing (blue) all adhered together and reinforced with cyanoacrylate cement then adhered to a square of nylon mesh on the bottom for the and liquid latex mold. Nylon mesh is connected to the bottom for tissue binding of subcutaneous tissue and a dab of silicone is applied to intercalation inside the animal. 4) Completed catheter ready for implantation (green). the exposed Silastic tubing to be used as an anchor for insertion DISCUSSION into the jugular vein. In light of these preliminary data, we have created a means ACKNOWLEDGEMENTS for acquiring stable mouse drug self-administration that is This work was supported by National Institute on Drug Abuse grant cost efficient, and can be applied to various acute or chronic R01-DA24040 (to D.C.C.), NIDA K award K-01DA017750 (to experimental drug paradigms. Our data show that this simple self- D.C.C.) administration setup is capable of generating consistent behavior and reinforcement for rewarding substances. Considering the PROGRESS AND COLLABORATIONS difficulties typically involved in intravenous self-administration To see up-to-date progress or if you are interested in contributing to mouse models, this setup is ideal for behavioral experiments this project visit www.neuro-cloud.net/nature-precedings/pomrenze investigating the reinforcing properties of self-administration in w.neuro-cloud.net/nature-precedings/pomrenze murine transgenic subjects. The dose-response data indicate that We are interested in establishing new collaborations in the drug significant effects of different doses are attainable through the self-administration field. For those interested in obtaining our consistent and reliable delivery of the drug. This indicates that the customized mouse or rats sized catheters and tethers for research mice were titrating the level of cocaine reward by adjusting their please visit www.neuro-cloud.net/nature-precedings/pomrenze ongoing nose-poking behavior within the session. The basis for any drug dependence study is initial, stable responding or drug 1. Kelley, B.M. et al. (1997). Phys and Behv, 62(1): 163- seeking behavior. Once established, experimental manipulations 167. such as stress, conditional gene knockout, or optogenetic control 2. Thomsen, M. et al. (2006). Psychopharm, 184: 145- of specific neural circuits can be imposed. The potentiation of 154. VTA synapses after active cocaine intake compared to passive 3. Chen, B.T et al. (2008). Neuron, 59: 288-297 . intake indicates that the rapid pharmacokinetics of IV delivery 4. Caine, S.B. et al. (1999). Psychopharm, 147: 22-24. cA Attribution 3.0 2011 Nature Precedings Page 2 of 2