Combined action of thioperamide plus scopolamine, diphenhydramine, or methysergide on memory in mice

The aim of the present experiments was to test the role played by the inter action of the selective H-3 receptor antagonist, thioperamide, with the cho linergic, histaminergic, and serotonergic systems in modifying memory. The behavioral tests used (open-field and passive-avoidance repetition) were se lected on the basis of the action displayed by thioperamide in these behavi oral situations. Posttrial administration of thioperamide (5 mg/kg) resulte d in an improvement in memory consolidation, as tested in the repetition of the open-field test, but repeated posttrial administration of thioperamide (2 or 5 mg/kg) had no effect in the repetition of passive avoidance test. Scopolamine (2 mg/kg) caused a deterioration in the memory processes in bot h tests; this effect was blocked by 2 mg/kg of thioperamide, which was itse lf ineffective in the test. These results may suggest that both the improve ment in memory due to thioperamide and its antagonism of the amnestic effec ts of scopolamine are determined by activation of central cholinergic syste ms, due to thioperamide inhibition of H-3 heteroreceptors. Diphenhydramine (2 or 10 mg/kg) was itself ineffective in the tests, but counteracted the m emory improvement caused by thioperamide in the repetition of the open-fiel d test. The effect of diphenhydramine is discussed in terms of interactions between histaminergic and cholinergic systems. Methysergide counteracted t he effect of thioperamide in the open-field test only at a high dosage (50 mg/kg). The possible implication of serotonergic systems on the effects of the methysergide-thioperamide interaction in the memory process is discusse d. (C) 1999 Elsevier Science Inc.