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N is for Neuroscience

Runway Model Rats’ Drug Lust


Thursday, June 28, 2007

This week in my tireless hustle to be oh-so clever with the calendar, I saved a day to play with my more curious side. I decided to step into a realm that I rarely approach, that which concerns itself with the table of elements and the Pythagorean theorem, science. Yikes! you say, and yeah, I know, but I did my best to find someone who studied something that everyone would find fascinating, like sex, drugs, and well, ourselves. So I went to the UCSB Neuroscience Department and found a real cerebral master to feed our craving for answers to our crazy curiosities.

Follow along as I, Right Brain Rita, attempt to make the most of my one opportunity to get left-sided brainiac Aaron Ettenberg to reveal more about his studies of Pharmacology and Neuroscience in a more lax and slightly inappropriate manner. Ettenburg is a Professor of Psychology at UCSB. He received his doctorate in Psychopharmacology and is an active member of the Neuroscience & Behavior graduate training program, among many other accomplishments and honors.

Can you briefly describe to us your studies of pharmacology and its relationship to neuroscience?

Neuroscience is the study of the brain and nervous system, and it’s a very broad topic. In my laboratory, we are interested in learning how drugs of abuse alter the function of the brain — more specifically, we want to understand the brain systems involved in the hedonic effects of drugs and how the brain changes during the development of addiction. Ultimately, the goal of such work is to provide the basis for the development of effective medications for the treatment of people trying to break themselves of a drug habit.

After reading your list of “Select Publications” on the university website, and such descriptions as “in a runway model of intravenous cocaine self-administration,” what exactly is the scientific definition of a runway model? And do you see any sort of connection between that and what the rest of us know as runway models?

As it turns out, laboratory rats actually ingest virtually all the same drugs that we do! That’s right: nicotine, alcohol, cocaine, methamphetamine, heroin! Given the opportunity to self-administer these drugs, they will freely and voluntarily do so. It’s important, then, to try and understand how such drugs act in the brain of this relatively simple animal since it is likely to provide us with critical insights into how the same drugs are working in our own human brains. There are a number of different procedures that researchers use to mimic or “model” drug-abuse in the animal laboratory. In our lab, rats choose to run down a long (6 foot) straight alley and enter a goal box where the computer detects their presence and “rewards” them with an injection of drug (e.g., it could be heroin, or nicotine or cocaine, etc.). They do not have to run, they choose to! In humans, one of the most critical issues for our understanding of drug abuse and addiction is to figure out what brain regions are involved in the motivation to seek the drug at a time when the person is no longer under the direct influence of the drug. What causes the nicotine addict to light up that first cigarette [after a hiatus], or the heroin addict to crave [another] fix. Obviously if we can understand and then counteract that craving, we can go a long way toward helping the recovering addict break their drug-use habit. The issue at hand is, of course, inherently a “motivational” one since we are asking what factors drive or push or induce us to re-engage in drug ingestion behavior — what is motivating us to take the drug? In our laboratory, the speed with which the rat runs down the alley and enters the goal box once each day, tells us how badly it wants to get the drug again — it provides us with a reliable index of the animal’s motivation to seek the drug! We can then begin the process of investigating which brain areas are critical for this motivation to occur and even begin testing possible pharmaceutical treatments that might serve as a means of reversing the “cravings” of our laboratory animals.

What exactly is this C-fos that becomes irregular between sexually-naive and more experienced male rats when exposed to a fine-looking female rat?

To understand this work let me first explain our approach: We hypothesize that drugs of abuse produce their positive reinforcing/hedonic properties by artifically and profoundly activating brain systems that are normally activated by naturally occurring positive incentives in the environment — i.e., food, water, sex. Hence some of our research is geared toward understanding the neurobiology of hunger, thirst and sexual motivational states — again because these “normal” states are likely the ones artificially recruited during the self-administration of drugs of abuse. So how do we do this research? In several of our studies we examined the motivation of male rats to run down an alley to a goal box that had a receptive female rat in waiting (the female was on the opposite side of a glass barrier so that the male could see, smell and hear the female, but was unable to come in physical contact with her). We learned that — not surprisingly — male rats are inherently motivated to run for females (they run slower if there is a male target in the goal box, and slower still if there’s nothing in the goal box). So what brain areas are activated in the male rats running an alley to gain access to a goal box with a waiting female? To answer this question, we conducted several neurochemical studies in which we measured the presence of a protein called c-FOS which increases inside brain cells when cells receive lots of electrical signals from other brain cells. It therefore provides us with an indication of which cells are most activated during a particular experience. In the case of males running for females, the brain sites that exhibited the largest increases in c-FOS concentrations were cells within a specific set of brain region related to a specific neurotransmitter (dopamine) — the same sites that are directly activated by ingestion of any one of several different drugs of abuse! Thus the motivation to seek drugs and the motivation to seek sexually receptive females, appears to involve the activation of the same cells within the brain!

Nicole de Ayora is a recent UCSB graduate who double-majored in English and Spanish with a minor in Art History. Now working as the listings editor for the Independent, De Ayora remains curious about all sorts of things.

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