Effects of Lateral Hypothalamic Injections of Glutamate Receptor Antagonist (D-AP5) and Agonist (ATPA) on Food Intake in Rats Under Simulated Microgravity

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Effects of Lateral Hypothalamic Injections of
Glutamate Receptor Antagonist (D-AP5) and Agonist
(ATPA) on Food Intake in Rats Under Simulated
Microgravity
Project Leader Katie Kavanagh
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What brain mechanisms underlie sensory specific
satiety in hind limb unloaded rats?
Questions

• Specifically, are lateral hypothalamic glutamate
  receptors regulating sensory specific satiety?

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Why is this important?

• We hope to determine what brain mechanisms
  regulate SSS and whether they operate similarly
  in microgravity as they do on Earth.

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Neural Model

• Hypothesis 1 D-AP5 will suppress food intake and
  increase latency to feed during a SSS paradigm in
  hind limb unloaded rats

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Neural Model

• Hypothesis 2 ATPA will boost food intake and
  decrease latency to feed during a SSS paradigm in
  hind limb unloaded rats

• How do we target glutamate receptors in the
  lateral hypothalamus?

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Getting to the Lateral HypothalamusStereotaxic
Surgery
(Paxinos and Watson, 1998)
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Methods Central Microinjections

• Procedure Inject 0.3 mL of
• aCSF (control)
• D-AP5 (10 nmol)
• n 9 male Sprague-Dawley rats

ATPA Study (unilaterally)
D-AP5 Study (bilaterally)

• aCSF (control)
• ATPA (1 nmol)
• n 8 male Sprague-Dawley rats

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Experimental Procedures

• 18 hr. food deprivation
• Pre-injection meal 90 minutes
• Rat Chow
• Lateral Hypothalamic injection aCSF, ATPA, or
  D-AP5
• Post-injection meal 60 minutes
• Rat Chow or Froot Loops

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Experimental Time Line
Rats had ad libitum access to food and water
except on experimental days. Light cycle was 12
hr /12hr light/dark.
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How SSS was measured

• Cumulative Food Intake (grams)
• pre-injection meal at 60 and 90 minutes
• post-injection meal at 30 and 60 minutes
• Latency to Eat (minutes)
• post-injection meal

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Results for D-AP5, a glutamate receptor
antagonist
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D-AP5 pre-injection meal data
Rats satiate on chow in pre-injection meal
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D-AP5 post-injection meal food intake at 30
minutes
Injection

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D-AP5 latency to eat in post-injection meal
Injection
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Summary D-AP5

• D-AP5, a glutamate receptor antagonist,
  suppresses Froot Loops intake and increases
  latency to feed when injected into the lateral
  hypothalamus.

• Conclusion
• D-AP5 suppresses intake of a highly palatable
  food suggesting that glutamate receptors in the
  lateral hypothalamus are part of the neural
  pathway underlying SSS.

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Results for ATPA,a glutamate receptor agonist
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ATPA pre-injection meal data
Rats satiate on chow in pre-injection meal
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ATPA post-injection meal food intake at 60
minutes
Injection
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ATPA latency to eat post-injection meal
Injection
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Summary ATPA

• ATPA, a glutamate receptor agonist, boosts rat
  chow but not Froot Loops intake when injected
  into the lateral hypothalamus.
• Conclusion
• Offering Froot Loops or injecting with ATPA
  appear to be equally effective in increasing food
  intake. This suggests that access to a highly
  palatable food is sufficient to saturate this
  neural pathway.

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Conclusions
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Application

• Although pharmacological interventions are not
  plausible, it appears that offering astronauts a
  more palatable food as second course is
  sufficient to ensure adequate intake.

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Results DAP-5 Suppresses Overeating During
Sensory Specific Satiety
Cumulative Food Intake (grams)
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Results Rats are Fed to Satiety on
Rat Chow
Cumulative Rat Chow Intake (grams)
_at_ 60 min
_at_ 90 min
Meal Duration
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D-AP5 Pre-injection meal food intake at 60 and
90 minutes
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ATPA Pre-injection meal food intake at 60 and 90
minutes
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D-AP5 post-injection meal food intake at 60
minutes
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ATPA Post-injection meal food intake at 30
minutes
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Summary aCSF

• Our results confirm that rats exhibit SSS during
  hind limb unloading
• Conclusion
• The same mechanisms responsible for SSS in
  horizontal rats appear to be operating in hind
  limb unloading