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Effect of dihydroergotoxine and cholinomimetics on passive avoidance behaviour in rats with disruption of cortical cholinergic innervation

The nucleus basalis magnocellularis (NBM) is the source of cholinergic afferent fibers innervating the rat neocortical regions. It has been known that intact cholinergic system is a prerequisite to unimpaired performance in learning and memory tasks. Therefore lesions of then NBM cause a marked loss of cognitive functions. There are some evidences that dihydroergotoxine (DHE) can also influence cholinergic neurotransmission activity (Le Poncin-Lafitte et al., 1985 ; Amenta et al., 1988). Lecithin is a precursor of acetylcholine and arecoline is direct muscarinic agonist. The purpose of this study was to analyze the influence of mentioned drugs on passive avoidance behaviour in rats with the NBM lesions. Bilateral electrolytic NBM lesions were made on Wistar albino rats weighing 350-450 g. The coordinates for the NBM lesions were 1.8 mm anterior to the bregma, 2.5 mm lateral to midline and 7.0 mm below the dura. 15 days after the surgery the rats started passive avoidance test per the procedure of Ashford and Jones (1976). A chamber with a electrified grid floor was used. The central area of the floor contained a wooden platform. Each rat was placed on the platform and left in the apparatus for 3 min. The total time spent on the platform was recorded. A total of 4 consecutive daily sessions were given. Passive avoidance behaviour in the NBM lesioned rats under the influence of various drugs was measured. The control animals received 0.9% solution. Other rats received DHE methanesulfonate (0, 01 ; 0, 1 ; 1 ; 10 ; 50 mg/kg or lecithin (250 mg/kg) or arecoline hydrochloride (1 mg/kg) or the combinations of mentioned cholinornimetics with DHE (0, 1 mg/kg) All tested drugs were given intraperitoneally, once per day in the course of 4 testing days. Arecoline had been injected 10 and lecithin and DHE 60 minutes before the passive avoidance experiment started. The results of our experiments indicate that: 1.) among the tested doses of DHE only the dose of 0.1 mg/kg caused mild, but not statistically significant improvement in passive avoidance behaviour in the NBM lesioned rats and that 2.) lecithin and arecoline alone or in the combinations with tested dose of DHE were effective in reversing the memory deficits in rats with lesions of the NBM.

dihydroergotoxine; lecithin; arecoline; passive avoidance; memory deficits; rat

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