This is a guest post by Martina Mustroph, one of Greta’s top student writers for Spring 2007
Rats are often useful models for understanding human behavior,. Testing drugs on rats before testing them on humans is particularly enticing because it is relatively free of ethical concerns (relative to drugging humans, at least), and the amount of drug required to achieve an effect is relatively small compared to the amount it would take to see an effect in a human. As rats’ nervous systems are very similar to the human nervous system, they lend themselves really well to drug studies. Rats have been used to study drug addiction for years.
Why bother doing drug research on rats in the first place? It is important to learn more about the mechanisms of human drug abuse because with additional knowledge about the mechanisms of drug abuse, drug rehabilitation programs can be improved, and risk factors in at-risk-individuals can be identified. Similarly, protective factors against drug abuse can be identified. Once protective factors are identified, we can implement policies that foster the development of these protective so that drug addiction and its associated problems (including its enormous costs to society) never develop in the first place. One suspected protective factor against drug addiction is environmental enrichment. Let us consider what environmental enrichment is. Environmental enrichment means that during development, the environment is stimulating. For a rat, this might mean growing up with other litter mates in a cage that is full of novel objects that are switched up every few days.
Building on past drug studies with rats, N.T. Bardo led a team in investigating whether environmental changes affect how rats use amphetamine. Amphetamine is highly addictive, and therefore you can see addictive behavior develop in a very short period of time. Bardo and his colleagues took 21-day-old rats that they had obtained and randomly assigned them to be raised in one of three different cage conditions: an enriched cage condition that contained novel objects and social partners (litter mates), a social cage condition that contained social partners only, or an isolated cage condition that contained neither objects nor social partners. After the rats had lived in their assigned condition for 45 days, the team removed food from the rat cages and waited until the rats’ body weights had fallen to 85% of their free-feeding body weight. They then installed two levers in each rat cage. One lever (Lever 1) dropped a pellet of sucrose into the cage when pressed. The other lever (Lever 2) was inactive; nothing happened when it was pressed. At first, the rats were rewarded with a sucrose pellet every time they pressed Lever 1. This was gradually increased until they were only rewarded every 5th time they pressed Lever 1. After this, the rats were again given free access to food in their cage. The type of system on which the rats were rewarded for pressing Lever 1 is called a “fixed ratio (FR) schedule,” and all it means is that every nth time is reinforced. (So an FR1 schedule means that every response is rewarded with a sucrose pellet; an FR2 schedule means that every 2nd response is rewarded with a sucrose pellet; an FR3 schedule means that every 3rd response is rewarded with a sucrose pellet, and so on.)
After rats had been trained to press the lever, they underwent surgery. Each rat was implanted with a catheter attached to Lever 1 feeding amphetamine directly into their veins. After they had recovered from surgery, the rats were then allowed to self-administer amphetamine first on an FR1 schedule a number of times and then on a progressive ratio (PR) schedule. A progressive ratio schedule is really an FR schedule where every nth response is rewarded, but where the n does not remain the same, like in an FR schedule, but keeps increasing. (So, for example, at first, every response is rewarded, then every 2nd response, then every 4th response, then only every 16th response, and so on.)
A progressive ratio (PR) schedule is, as has probably occurred to you, less reinforcing than a fixed ratio (FR) schedule, because it takes increasingly more effort to obtain the same reward. This is exactly what makes the PR schedule a better indicator of addictive behavior, too, since a rat that keeps responding on a PR schedule is putting in increasingly more effort to obtain a reward. The FR schedule was first used in all runs, however, because it is the best way to train rats to use the lever.
Now, remember Lever 2, which was an inactive lever and did not deliver anything when pressed? The researchers counted how many times each of the three groups of rats pressed Lever 2 to get a baseline measurement of how active each group of rats was. This was done in case one group self-administered significantly more or less amphetamine than any of the other two groups, that they could be sure that this was not just due to this rat group being more or less active in general than the other two rat groups. In fact, all three groups of rats (environmentally enriched, socially enriched, and isolated) pressed the inactive lever the same number of times at first, and that this rate of pressing declined equally steadily among all three groups. Since the only way in which the three rat groups differed was their environment placement, the team could also be sure that this effect was due to the rats’ environment during development.
What did they find? For the sucrose reward task, regardless of sex or rearing group, number of pellets earned decreased as the FR value increased. This makes sense because with an increased FR value, the rats had to work harder to get a pellet. Environmentally enriched rats at first earned more sucrose pellets than the isolated condition rats, and this difference among the two rearing groups was more pronounced in female rats than in male rats, but this discrepancy evened out completely with successive FR sessions.
There were no sex differences in the amount of amphetamine used. There was not even a significant difference between the environmentally enriched, socially enriched, and isolated rats in the number of amphetamine infusions earned when the amphetamine infusion was of a high dose (0.1 mg/kg/infusion) each time.
But when the amphetamine infusion was of a low dose (0.03 mg/kg/infusion) each time, there was a significant difference between the three rearing conditions:
The environmentally enriched rats used less amphetamine than the isolated condition rats did as the study progressed, as did the socially enriched rats. However, the socially enriched rats did use more than the environmentally enriched rats.
At the higher dose of amphetamine, the environmentally enriched and the socially enriched rats pressed lever 1 more often than they did with the lower dose of amphetamine:
Yet for the isolated condition rats, their rate of response stayed the same at both doses.
The fact that the environmentally enriched rats and the socially enriched rats showed similar patterns of response behavior to amphetamine infusions and the fact that they self-administered less amphetamine than the isolated rats suggests that environmental and social enrichment during development somehow worked as a protective factor against addiction to amphetamine. The drug amphetamine simply was not as enticing to the environmentally enriched and to the socially enriched rats as it was to the isolated condition rats. The fact that no difference in amphetamine administration was seen between rearing conditions for the higher dose of amphetamine may suggest that with strong drugs, environmental and social enrichment are not strong enough protective factors against drug abuse.
Presumably, the overall response pattern seen in the rats would also be seen in humans who have been raised in environmentally enriched (speak: stimulating) environments and in socially enriched environments (with peers) as opposed to humans who have been raised in relative seclusion. It is by now becoming clear that environmental enrichment does protect against drug abuse vulnerability. Since there is much conflicting evidence about the effects of environmental enrichment, it is still too soon to make definitive statements about exactly how environmental enrichment serves as a protective factor against drug abuse vulnerability. Further research is needed to clarify the role that environmental enrichment plays. Meanwhile, go thank your younger sibling(s) for being their clingy little selves all those years ago. Chances are: You’re probably still indirectly experiencing the benefits of this today; they were your environmental enrichment.
Bardo, M.T., Klebaur, J.E., Valone, J.M., & Deaton, C. (2001). Environmental enrichment decreases intravenous self-administration of amphetamine in female and male rats. Psychopharmacology, 155, 278-284.