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Our research is focused on defining the brain mechanisms that control
eating behavior. We hope to learn how the normal and abnormal function
of these mechanisms contribute to natural eating behavior, as well
as to disturbances of eating behavior and body weight control.
Equally important, we hope to reveal principles of neural integration
that are relevant to a broad range of brain functions. The type
of questions we ask are: which physiological and environmental factors
are responsible for activating eating-control neurocircuits; what
are the specific neural pathways and neurotransmitters which comprise
these circuits and; what are the behavioral/physiological consequences
of their activation? We are using three complementary approaches
to address these issues in animals as described below.
Central Microinjection. Minute quantities of certain neurotransmitters,
when injected directly into specific brain areas, can cause animals
to perform complex behaviors similar to those that occur naturally.
For example, we have shown that microinjections of neuropeptide
Y into specific areas of the hypothalamus can cause animals to eat
and, with chronic stimulation, to develop massive obesity. By determining
which neurotransmitters act similarly and the brain areas where
they are effective, we can begin to reveal the specific neurochemicals
and brain sites involved in controlling eating behavior and body
weight gain.
Measurement of Neurotransmitter Release. Here, instead of modulating
brain chemistry and then measuring the corresponding changes in
behavior, we manipulate the animal's behavior and then use biochemical
techniques to measure the corresponding changes in brain chemistry.
For example, we have shown that norepinephrine, another neurotransmitter
that causes eating when injected into a certain brain area, is also
normally released from this same brain area during natural eating
behavior.
Imaging Brain Activity. More active brain areas have higher
metabolic rates. Therefore, we can use metabolic imaging techniques
to derive a picture of the specific brain areas activated during
eating behavior. Using this approach, we are identifying the neuronal
sites and brain pathways which are activated by central neurotransmitter
injections that produce eating, as well as those naturally activated
during this behavior.
SELECTED PUBLICATIONS
Duva, M.A., Tomkins, E.M., Moranda, M., Kaplan, R. Sukhaseum, A., Jimenez, A. & Stanley, B.G. (2001) Reverse microdialysis of N-methyl-D-aspartic acid into the lateral hypothalamus of rats: effects on feeding and other behaviors, Brain Research, 921, 122-132.
Blevins, J.E. Stanley, B.G. & Reidelberger, R.D. (2002) DMSO as a vehicle for central injections: Tests with feeding elicited by norepinephrine injected into the paraventricular nucleus, Pharmacology Biochemistry and Behavior, 71(1-2), 277-282.
Duva, M.A., Tomkins, E.M., Moranda, L.M., Kaplan, R., Sukhaseum, A., Bernardo, J.P. & Stanley, B.G. (2002) Regional differences in feeding and other behaviors elicited by N-methyl-D-aspartic acid in the rodent hypothalamus: a reverse microdialysis mapping study, Brain Research, 925, 141-147.
Hettes, S.R., Gonzaga, J. Heyming, T.W., Perez, S., Wolfsohn, S. & Stanley, B.G. (2003) Dual roles in feeding for AMPA/kainate receptors: receptor activation or inactivation within distinct hypothalamic regions elicits feeding behavior, Brain Research, 992, 167-178.
Khan, A.M., Cheung, H.H., Gillard, E.R., Palarca, J.A., Welsbie, D.S., Gurd, J.W., and Stanley, B.G. (2004) Lateral hypothalamic signaling mechanisms underlying feeding stimulation: Differential contributions of Src family tyrosine kinases to feeding triggered either by NMDA injection or by food deprivation. Journal of Neuroscience, 24(47), 10603-10615.
Duva, M.A., Siu, A., and Stanley, B.G. (2005) Antagonist of NMDA receptors alters lipoprivic eating elicited by 2-mercaptoacetate. Physiology and Behavior, 83, 787-791.
Duva, M.A., Tomkins, E.M., Moranda, L.M., Kaplan, R., Sukhaseum, A., Stanley, B.G. (2005) Origins of lateral hypothalamic afferents associated with N-methyl-D-aspartic acid-elicited eating studied using reverse microdialysis of NMDA and Flurogold. Neuroscience Research, 52(1), 95-106.
Lee, S.W. & Stanley, B.G. (2005) NMDA receptors mediate feeding elicited by neuropeptide Y in the lateral and perifornical hypothalamus. Brain Research, 1063, 1-8.
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