Sleep-wake effects of meta-chlorophenyl piperazine and mianserin in the behaviorally depressed rat

In paper citation: (Mavanji, Meti, & Datta, 2002)

All rats in this paper were made depressed using neonatal clomipramine treatments. All rats were male. Controls were treated with saline, but handled in the same manner.

The new findings from this paper are:

1. REM sleep onset latency is significantly shorter in depressed rats than in controls. Rats spend ~25% less time in SWS before their first REM cycle.
2. The total number of REM sleep episodes is significantly (~2X) higher in depressed rats than in controls.
3. The total amount of REM sleep in depressed rats is significantly more than controls (>2X more REM).
4. mCPP, a serotonin agonist, decreased the total amount of REM sleep in the depressed rats by decreasing the total number of REM sleep episodes and increasing the REM sleep onset latency.
5. mianserin, a SSRI, decreased the total amount of REM sleep in the depressed rats by decreasing the total number of REM sleep episodes. 

Other important information:

• REM sleep deprivation in humans alleviates symptoms of depression (Vogel et al., 1975).
• REM sleep deprivation in rats normalizes deficits in sexual activity and aggression, which are symptoms of rat depression (Vogel et al., 1990).
• mCPP is known to increase serotonin release (Bauman et al., 1993) and reduce REM sleep in humans ( Lawlor et al., 1991).
• Clomipramine treated rats have less serotonin in their brain than control rats (Mavanji & Meti, 1999).
• Serotonin inhibits REM sleep (McCarley, 1982) and so serotonin agonists reduce REM sleep (Quattrochi et al., 1992; Stickgold et al., 1993)
• mCPP normally reduces REM in the controls if it is injected systemically because it inhibits acetylcholine release (Vizi et al., 1981) It didn't in this case because it was injected  ICV.
• Mianserin typically reduces REM in both depressive patients and normal subjects (Mendlewicz et al., 1995; Tormey et al., 1980).

Remaining questions:

• How does the clomipramine rat model work? Would this still be the case in social stress depressed rats, or learned helplessness rats?
• The CLI+mianserin group seemed to have low wakefulness and high SWS in my opinion. I'm surprised that it didn't come out significant.