University of Alberta

Year: 1990

Animal models of human amnesia and dementia: hippocampal and amygdala ablation compared with serotonergic and cholinergic blockade in the rat

PMID: 2288673

Dickson CT, Vanderwolf CH

Behav. Brain Res. 1990 Dec;41(3):215-27

Abstract

The behavioral effects of combined bilateral hippocampal and amygdala ablation (previously proposed as a model of human global amnesia) were compared to those seen with central blockade of the ascending cholinergic and serotonergic projections (a possible model of human global dementia) in male hooded rats. Rats were prepared with: (a) bilateral surgical lesions of the hippocampus and amygdala; (b) pharmacological blockade of central cholinergic and serotonergic function by systemic injections of scopolamine and p-chlorophenylalanine; and (c) neurotoxic lesions of the rostrally projecting serotonergic nuclei in the brainstem using intracerebral injections of 5,7-dihydroxytryptamine, later combined with scopolamine. The behavioral tests used were: an open field test, a swim-to-platform test, and a Lashley III maze. In all 3 tests, rats with either the neurotoxin lesions plus scopolamine or p-chlorophenylalanine plus scopolamine treatment showed greater impairments in comparison with controls than did the combined lesion group. These results indicate that simultaneous blockade of central serotonergic and cholinergic transmission has a greater effect on some aspects of the organization of behavior than large surgical lesions of the hippocampus and amygdala.

Effects of p-chlorophenylalanine and scopolamine on retention of habits in rats

PMID: 2140608

Vanderwolf CH, Dickson CT, Baker GB

Pharmacol. Biochem. Behav. 1990 Apr;35(4):847-53

Abstract

Rats were trained on a conventional maze test or on a swim-to-platform test. Retention of swim-to-platform performance 7 days later was severely impaired by posttraining treatment with a combination of p-chlorophenylalanine (PCPA) and scopolamine although neither drug alone had any effect. Retention of the maze habit was moderately impaired by scopolamine alone and severely impaired by a combination of scopolamine and PCPA, but was unaffected by PCPA alone. Polygraphic recordings confirmed previous reports that a combination of PCPA and scopolamine can abolish neocortical low voltage fast activity and hippocampal rhythmical slow activity. Combined blockade of central cholinergic and serotonergic neurotransmission in rats may provide a useful animal model of Alzheimer’s disease.

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