Effects on 5-HT and Ach in the Rat by the I.C.V Injection of PCPA

PCPA is a drug which depletes serotonin by inhibiting tryptophan hydroxylase activity.

Recent evidence indicates that the ascending cholinergic projection from the basal forebrain and ascending serotonergic projections from the brain stem exert a powerful control over the generalized electrical activity of the hippocampus formation and neocortex. Cross & Dentin(1985) reported that destruction of ascending cholinergic neurons by injection of ibotenic acid into the basal forebrain results in a significant reduction in 5-HT₁ receptor in the denervated cortex.

Maura & Raiteri(1986) observed that the release of (³H) Ach was concentration depenendently inhibited by exogenous 5-HT in rat hippocampus.

So, we were interested in investigating whether PCPA which depletes the serotonin also affects the cholinergic system. The brain(cortex area 3, 4, 17 and hippocampus) were exised on the 3day and the 7day after single injection of PCPA 3mg/10µl into the cerebroventricle(Lateral ventricle AP+8.2mm ; L, 1.5mm ; DV+1.2mm).

5-HT and 5-HIAA contents were measured by HPLC-ECD and acetylcholine was measured by GC.

The results are

1) 5-HT & 5-HIAA contents in the cortex & hippocampus were decreased gradually after PCPA injection but not significant.

2) Ach contents in the cortex & hippocampus were decreased significantly on the 3rd day & 7th day after PCPA injection.

3) We observed that the cerebral cortex has small amount of vesicles or no vesicles and coated vesicles in the axon terminals by electron microscope.

So, these results suggest that PCPA treatment results in significant changes of cholinergic system in the brain.