MBG 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 LiCl (0.15M, 20 ml/kg, i.p.) administration in selenate-pretreated vs control rats.

Agenda

The first set of LOB experiments (MBF01-06) determined that a 20 ml/kg i.p. injection of 0.15 LiCl reliably induces LOB behavior in male Sprague Dawley rats within 30 minutes.

• The low dose of LiCl (0.15M, 6 ml/kg, i.p.) did not induce LOB behavior
• The moderate dose of LiCl (0.15M, 12 ml/kg, i.p.) reliably induced pica but did not induce LOB in all of the rats.

MBG01-08

• A 0.5mg/ml solution of sodium selenate in 0.15M NaCl was prepared the day before the experiment.
• Male Sprague Dawley rats (n=8/group) were given selenate (1 ml/kg, i.p.) or NaCl (0.15M, 1 ml/kg, i.p.) two hours before receiving LiCl (0.15M, 20 ml/kg, i.p.) or NaCl (0.15M, 20 ml/kg, i.p.).
• Immediately after the LiCl injections, rats were placed in a test cage and video recorded for 30 minutes.
• Recordings were stopped after 30 minutes and the rats were returned to their home cages.
• Videos were scored for the time to onset of LOB for all rats.

Results

• Selenate pretreatment did not affect the time to onset of LOB.
• Two-way ANOVAs with pretreatment (vehicle or selenate) and LiCl condition (LiCl or NaCl) as factors revealed a significant effect of LiCl condition, but not pretreatment, on time to LOB onset (F[1,28] = 35.15, p<1e-05).

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