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the lateral hypothalamus (LH), which is one of the centers for reward behavior and
sensations [11] .
13.3 Reward Center/Pleasure and NK Cells
13.3.1 Lateral Hypothalamus
Wenner et al. found that NK cell activity in Wistar-King-Aptekman (WKA) and
SD rats was significantly higher following electrical stimulation of the LH as com-
pared to animals that underwent sham operations [8] . There was no such differ-
ence between sham-operated rats and those receiving electrical stimulation in the
frontal cortex as a control. Operations were performed under sodium pentobarbital
anesthetic, and NK activity against YAC-1 target cells was measured 20 hours later
using the 51 Cr release assay. Because the LH area stimulated in these experiments
is a potent reward center, and stimulation of this point increased NK activity, it has
been suggested that pleasure plays a role in cellular immunity. Later, Iimori et al. [9]
showed that electrical stimulation of the LH in rats increased splenic NK cell activ-
ity, whereas electrical ablation of the LH decreased it. However, the percentage of
NK cells in the spleen, as detected by the anti-NKR-P1 monoclonal antibody (mAb),
did not change significantly. These results suggest that the LH does not modulate
splenic NK cell activity by increasing NK cell numbers, but rather by increasing NK
cell activity. In addition to the acute electrical stimulation of the LH of anesthetized
rats, Wenner et al. [10] showed that splenic NK cell activity was significantly higher
following chronic, uncontrollable electrical stimulation of the LH in fully conscious
rats, compared to sham-operated rats [10] . All rats demonstrated that the electrode
site had self-stimulating properties, which supports the possibility that the experience
of reward may be implicated in NK cell activity augmentation.
Recently, Wrona and Trojniar and Wrona et al. [12,13] tested the effects on both
spleen and blood NK cells of acute (1 day) and chronic (21 days) electrical stimu-
lation of the LH, and examined large granular lymphocyte (LGL) numbers in con-
scious, freely behaving animals. Chronic stimulation of the LH caused significant
augmentation of NK cell activity. Rats responding to LH stimulation with feeding
showed a slightly greater effect than those responding with a locomotor reaction. The
observed effects were anatomically specific. The involvement of the LH in reward
phenomena was shown to be associated with NK cell augmentation as well.
13.3.2 Ventral Tegmental Area
It was also discovered that chronic electrical stimulation of the midbrain ventral teg-
mental area (VTA) increases spleen NK cell cytotoxicity in rats [14] . The LH belongs
to the so-called brain reward system, a collection of the central structures the activa-
tion of which produces positive emotions. The midbrain VTA is another prominent
reward-relevant structure. In the present work, chronic electrical stimulation of the
VTA (constant current 0.1-ms duration cathodal pulses delivered at frequency 50 Hz
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