Friday, January 14, 2011

How do rats become addicted to cocaine?


Cocaine

You guessed it: Cocaine.


The title says it all. Sure, people might do cocaine for a variety of reasons, such as availability, curiosity, or for social acceptance within a group of peers that uses the substance. In my post from Wednesday, I discussed the effects of cocaine on the brain, and the changes that occur as a result of using the drug. Today I want to discuss how rats in a lab "do" cocaine, since it's clear they can't do this:


So here is the deal. If you know anything about or operant conditioning, then you will follow what I am about to describe. If you are not familiar with operant conditioning, here is a good link for a refresher course on behaviorism. Operant Conditioning

First, rats are not given food for approximately one day, so that they will be hungry when first placed in the operant box for what we call "food training." Here is a picture of the operant box:

A lever is extended out from both sides, but only one side actually does anything. Here, we are saying that is the right side. So, the rat is curious and moving about in the cage, and presses the lever on the right side. A light comes on above the lever, a tone sounds, and most importantly, he is rewarded by a pellet of food that is released for him. He thinks to himself how cool that was, and tries it again on the left side. No such luck. Tries the right side again, and sure enough: a pellet of food is released following the tone and light paired cue.

The rat spends 15 hours in the operant box, which is enough time (for most rats) to put two and two together, thus realizing that pressing the right lever results in a reward.

Okay, so he realizes that the right lever equates to a reward. What does this have to do with drug administration? I'm getting there.

The rat has a catheter on its back, which looks like a backpack. Here is a similar, but not exact design:

[I'm getting a little ahead of myself, but as an FYI, in many cases, the rat also has a cannula on its brain, so that after it is killed, the investigator is able to examine the brain histology.]


The rat has a catheter that is hooked up to an infusion pump that is filled with cocaine.




It is similar to the above picture, but that the levers are still present, and the rat only receives an infusion of cocaine when he presses the right lever. Once again, a light and a tone are cues that come on as the infusion of cocaine is being delivered. 

Most of the rats end up liking the infusion, and thus, continue to press the lever and receive more cocaine. I should note that there are certain precautionary measures that are placed to keep the rat from overdosing on the cocaine. For example, after receiving one infusion, the rat has to wait 30 seconds before it is able to get another "hit." Even if the rat presses the lever during this "time out" period, there will be no drug administered. Also, after receiving a certain amount of infusions per session the rat is cut off. As my mentor Kate says, "The party's over." This keeps them from having a cocaine hangover, and thus generating a negative response to the drug. Having an aversive effect to cocaine would hinder the animal in its later cocaine sessions, and as a result, he would not be very enticed to try the drug at a later time.

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