Biology Reference
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the idea that there is a relationship between cytokines and sensory pleasure, they may
also be interpreted as being due to an increase in “finickiness” rather than anhedonia.
For example, LPS-treated rats had the same hedonic patterns in response to sucrose as
controls, whereas animal models predictive of a reduction in hedonism (e.g., models
of depression) are characterized by a decrease in sucrose preference and ingestion.
Feeding is regulated on the basis of the taste and composition of nutrients, and
there is a significant correlation between the sweet taste of food and its calorific
value, and between the bitter taste of food and its toxicity. The attraction to sweet
nutrients and aversion to bitter food are particularly important for an omnivore such
as the rat in terms of survival value, more so since the rat lacks the ability to elicit an
emetic reflex. The fact that LPS-treated rats responded to quinine in the same way
as controls could be interpreted as suggesting that sick rats are still able to reject
bitter-tasting foods. Conversely, LPS-treated rats still respond with positive appetite
to sucrose, suggesting that sickness does not interfere with the perception of hedonic
(ingestive) value. However, saccharine has a mixture of quinine- and saccharine-like
properties and LPS-treated rats will reject a concentration of saccharine that would
normally be ingested by controls. This may be interpreted as an increased sensitiv-
ity of LPS-treated rats to the aversive component of saccharine and/or a decreased
responsiveness to its hedonic component. This phenomenon would prevent sick ani-
mals from ingesting amounts of a potentially toxic compound that would normally
be tolerated by healthy animals. This interpretation fits with Cabanac's hedonic the-
ory of motivation, whereby hedonism supports behavioral responses to useful stimuli
and displeasure facilitates the avoidance of potentially dangerous stimuli
[36]
.
12.2.5 Cytokines and Cognitive Function
Infection or treatment with pro-inflammatory cytokines, such as IL-1 or IFN-,
can adversely affect cognitive function in humans and animals. Central or peripheral
administration of IL-1 can produce learning deficits by impairing retrieval of infor-
mation; for example, impairing performance on spatial memory tasks and interfering
with escape learning and enhancing fear conditioning. The latter can be blocked by
intracerebroventricular (ICV) treatment with IL-1ra prior to exposure to inescapable
foot shock
[37]
. Conversely, brain-derived neurotrophic factor (BDNF) in the hip-
pocampus plays a positive role in cognition, and intrahippocampal IL-1 can attenu-
ate the increase in BDNF mRNA in the hippocampal CA1, CA2, and dentate gyrus
(DG) regions that is normally induced following contextual fear conditioning
[38]
.
This effect of IL-1 may be direct, or may involve glucocorticoid effects, as the con-
centration of glucocorticoids is elevated following IL-1 administration, and the
detrimental effects of IL-1 on memory may be prevented by co-administering the
glucocorticoid receptor antagonist RU486
[39]
. IL-6 may adversely affect memory
processing, and IL-6 knockout mice exhibited a facilitation of radial maze learning
compared with wild-type mice, in terms of smaller working memory errors, faster
acquisition, and a higher percentage of animals attaining the criterion
[40]
. IL-2 also
plays a role in cognition, and mice deficient in this cytokine exhibit defects in spatial
learning and memory when tested in the Morris water maze.
