MBF Selenate Lying on Belly

Selenate modulation of LiCl-induced Lying-on-Belly

Background

Sodium Selenate (Na2Se04) activates PP2A (1).

CTA and Selenate experiments show that male Sprague Dawley rats given systemic injections of 0.5mg/kg sodium selenate two hours before taste aversion conditioning form attenuated taste aversions that extinguish rapidly. Selenate also decreases LiCl-induced phospho-MAP kinase in the NTS and lateral PBN.

Results suggest that selenate interferes with the regulation of learning-induced intracellular signaling by PP2A, and prevents consolidation of memories acquired during CTA learning. However, an alternative explanation is that sodium selenate affects LiCl-induced malaise and prevents the rats from associating the conditioned stimulus (saccharin taste) with LiCl by dampening the effects of LiCl toxicity.

Rats typically display lying-on-belly (LOB) behavior in response to LiCl-induced malaise. The time to onset of LOB behavior has been shown to decrease as the dose of LiCl increases (2), so the time to onset of LOB can be used to infer the magnitude of LiCl-induced malaise. This experiment aims to determine if sodium selenate pretreatment weakens the toxic effects of LiCl by measuring the time to onset of LOB after injections of 20ml/kg, 12ml/kg and 6ml/kg LiCl (0.15M, i.p.) in selenate-pretreated vs control rats.

Agenda

  • A 0.5mg/ml solution of sodium selenate in 0.15M NaCl was prepared the day before the experiment.
  • Male Sprague Dawley rats (n=6/group) were given selenate (1 ml/kg, i.p.) or NaCl (0.15M, 1 ml/kg, i.p.) two hours before receiving 6ml/kg, 12ml/kg or 20ml/kg injections of LiCl (0.15M, i.p.) or NaCl (0.15M, i.p.).
  • Immediately after the LiCl injections, rats were returned to their home cages and video recorded for 30-60 minutes.
  • Videos were scored for the time to onset of LOB for all rats.
Drug Injection Summary
Subject Day1 (6ml/kg) Day2 (12ml/kg) Day3 (20ml/kg) Day4 (12ml/kg) Day5 (12ml/kg) Day6 (12ml/kg)
MBF01 NaCl/NaCl Sel/NaCl Sel/LiCl NaCl/LiCl Sel/LiCl NaCl/NaCl
MBF02 Sel/NaCl Sel/LiCl NaCl/LiCl NaCl/NaCl NaCl/LiCl Sel/NaCl
MBF03 Sel/LiCl NaCl/LiCl Sel/NaCl NaCl/NaCl Sel/LiCl Sel/NaCl
MBF04 NaCl/LiCl NaCl/NaCl NaCl/NaCl Sel/LiCl NaCl/LiCl Sel/NaCl
MBF05 NaCl/LiCl Sel/LiCl NaCl/NaCl Sel/NaCl NaCl/NaCl NaCl/LiCl
MBF06 Sel/LiCl Sel/NaCl Sel/NaCl NaCl/LiCl NaCl/NaCl Sel/LiCl

Results

References

Corcoran NM, Martin D, Hutter-Paier B, Windisch M, Nguyen T, Nheu L, Sundstrom LE, Costello AJ, Hovens CM. Sodium selenate specifically activates PP2A phosphatase, dephosphorylates tau and reverses memory deficits in an Alzheimer’s disease model. Journal of Clinical Neuroscience 17: 1025- 1033, 2010.[1]

Nunnink M, Davenport RA, Ortega B, Houpt TA. d-Cycloserine enhances conditioned taste aversion learning in rats. Pharmacology Biochemistry and Behavior 87(3): 321-330, 2007. [2]

People

Marena Bass