Ricerc@Sapienza

Paradoxical sleep deprivation in rats is considered as an experimental animal model of mania endowed
with face, construct, and pharmacological validity. We induced paradoxical sleep deprivation by placing
rats onto a small platform surrounded by water. This procedure caused the animal to fall in the water at
the onset of REM phase of sleep. Control rats were either placed onto a larger platform (which allowed
them to sleep) or maintained in their home cage. Sleep deprived rats showed a substantial reduction in
type-2 metabotropic glutamate (mGlu2) receptors mRNA and protein levels in the hippocampus, but not
in the prefrontal cortex or corpus striatum, as compared to both groups of control rats. No changes in the
expression of mGlu3 receptor mRNA levels or mGlu1 and mGlu5 receptor protein levels were found
with exception of an increase in mGlu1 receptor levels in the striatum of SD rats. Moving from these
findings we treated SD and control rats with the selective mGlu2 receptor enhancer, BINA (30 mg/kg, i.p.).
SD rats were also treated with sodium valproate (300 mg/kg, i.p.) as an active comparator. Both BINA and
sodium valproate were effective in reversing the manic-like phenotype evaluated in an open field arena
in SD rats. BINA treatment had no effect on motor activity in control rats, suggesting that our findings
were not biased by a non-specific motor-lowering activity of BINA. These findings suggest that changes
in the expression of mGlu2 receptors may be associated with the enhanced motor activity observed with
mania.