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quired, so the rat still finds it just as pleasurable. If the work requirement VITAMIN A: FRIEND OR FOE?
is low—for example, if the rat must only press the lever once or four times Vitamin A supports the production of
to obtain a pellet of the pleasurable food—then the dopamine-depleted arachidonic acid (see Figure 2) and supports the
rat will press the lever just as often as the normal rat. Even if weights are dopamine system more directly by stimulating
added to the lever so that the rat has to do more and more physical work, the production of dopamine receptors and at least
the dopamine-depleted rat will still do just as much work as the normal three other proteins involved in carrying out
rat. It is only when the rat must do work for a longer amount of time before the cellular response to dopamine. Research-
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obtaining its reward that the dopamine-depleted rat fails to perform. 24 ers have not examined the relationship between
The clearest demonstration of this finding was an experiment pub- vitamin A status and depression, but the physical
lished in 2001 in which rats were rewarded one pellet of preferred food for ailments with which such mental illnesses are
every fifty lever presses, but on different payment schedules. Normal rats associated are in turn associated with vitamin
would do just as much work to receive six pellets after 300 lever presses A deficiency. For example, the incidence and
as they would to receive one pellet after fifty lever presses. Dopamine- severity of Crohn’s disease and ulcerative colitis,
depleted rats, however, began doing much less work to receive two pellets the two most common forms of inflammatory
for every 100 lever presses and essentially ceased doing any work at all bowel disease, and the incidence and severity
when they were rewarded with four pellets for every 200 lever presses. of asthma in children, are all associated with
24
This experiment clearly showed that dopamine is a central regulator of deficient blood levels of vitamin A. 26-28 This
future-orientation and the willingness to sustain effort over time towards would lead many people to suggest that vitamin
a goal that will be achieved at some point in the future. A might be involved in preventing depression
Endocannabinoids thus not only prevent the anxiety and feeling of or anxiety. Recent literature reviews, however,
self-defeat that leads us to run from challenges rather than confronting suggest precisely the opposite—that vitamin A
them, but also help support the future-oriented maintenance of sustained causes depression. 25,29
effort that is necessary for personal financial and career success and a In fact, one review even acknowledged that
prosperous society. the actions of vitamin A on the dopamine system
are “the opposite to what would be expected for

FIGURE 4: 13-CIS-RA ENTERS NUCLEUS UNREGULATED

SOURCE: Ruhl and others. Embryonic subcellular distribution of 13-cis and all-trans-retinoic acid indicates differential
cytosolic/nuclear localization. Toxicol Sci. 2001;63(1):82-9.

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