This post is the sixth in a series that aims to educate readers about the tools that are used in neuroscience research. Previously we discussed Radioactive Binding Assays, Novel Object Recognition, Calcium Imaging and EEG.
Currently I am running a study that examines the effects of chronic nicotine on sensory processing in mice. While I don’t mind coming into the lab on weekends, the prospect of visiting my animals 24/7 to inject nicotine wasn’t exactly practical. I could give daily or twice daily injections, but even that doesn’t really come close to approximating the behavior of human smokers.
That’s why we turned to a company called Alzet that manufactures miniature pumps for drug delivery in laboratory animals. These pumps can deliver small volumes of drug solution at a controlled rate over a period of up to six weeks. We opted for the 2002 model, with a reservoir volume of 0.2 mL and a flow rate of 0.5 µL/hr.
They are pretty easy to use: Just fill up the reservoir with concentrated drug solution and pop on the cap. Then, anesthetize the rodent and cut a small slit in its back using standard aseptic techniques. After opening a small cavity for the pump with a hemostat, insert the device and close the opening using medical staples.
After implanting these pumps subcutaneously, I couldn’t help but wonder if these things were actually going to work. How could a little piece of plastic control the flow of drug solution so precisely? If they worked because of osmotic pressure, then shouldn’t the flow rate depend on the concentration of the dissolved drug? I knew that osmotic pumps were popular, but I couldn’t shake the irrational fear that these $20 devices were just one big scam.
The only way I could settle my nerves was by figuring out how the devices worked. Luckily Alzet’s website is relatively transparent about the mechanism. Now I know that the osmotic pressure difference is actually between the animal’s body and the “salt sleeve” that surrounds the drug reservoir. From their website:
ALZET pumps operate because of an osmotic pressure difference between a compartment within the pump, called the salt sleeve, and the tissue environment in which the pump is implanted. The high osmolality of the salt sleeve causes water to flux into the pump through a semipermeable membrane which forms the outer surface of the pump. As the water enters the salt sleeve, it compresses the flexible reservoir, displacing the test solution from the pump at a controlled, predetermined rate. Because the compressed reservoir cannot be refilled, the pumps are designed for single-use only.
The rate of delivery by an ALZET pump is controlled by the water permeability of the pump’s outer membrane. Thus, the delivery profile of the pump is independent of the drug formulation dispensed.
Pretty nifty, huh? Even niftier is the accompanying animation:
Now I am much more confident that my mice are indeed receiving the expected dose of nicotine. In retrospect my fears were misplaced, but in science it never hurts to be skeptical/cautious.