Evidence that serotonin mediates non-cholinergic neocortical low voltage fast activity, non-cholinergic hippocampal...

Previous research has shown that low voltage fast activity (LVFA) in the neocortex and rhythmical slow activity (RSA) in the hippocampus can result from activity in either of two ascending pathways. Activity in neurons in the basal forebrain may produce atropine-sensitive (presumably cholinergic) LVFA and RSA during both Type 1 behavior (e.g., head movement, walking) and Type 2 behavior (e.g., waking immobility, face-washing, tremor). Activity in an aminergic pathway may produce atropine-resistant LVFA and RSA during Type 1 behavior only. The role of 5-hydroxytryptamine (5-HT) in this pathway was studied in rats treated with p-chlorophenylalanine (PCPA; 500 mg/kg/day X 3, i.p.). Amine levels were measured by high pressure liquid chromatography with electrochemical detection. Brain slow wave and multi-unit activity was assessed by inspection and by a procedure of filtering and integration. PCPA treatment alone had little effect on LVFA or RSA, but following PCPA and atropine (50 mg/kg) together, both LVFA and RSA were attenuated or eliminated. Thus, atropine-resistant LVFA and RSA may be dependent on 5-HT transmission. A combination of PCPA and atropine produced a very severe deficit in performance in a simple water maze. Rats treated with this drug combination may provide an animal model of human global dementia.