Abstract
The effects of the administration of different 5-HT4receptor antagonists (SDZ 205557, GR 125487) and 5-HT4receptor agonists (BIMU 1, BIMU 8) on memory processes were evaluated in the mouse passive avoidance test. The administration of SDZ 205557 (10 mg kg−1 i.p.) and GR 125487 (10 mg kg−1i.p.) immediately after termination of the training session produced an amnesic effect. BIMU 1 (20 mg kg−1 i.p.) and BIMU 8 (30 mg kg−1 i.p.), administered 20 min before the training session, prevented the 5-HT4 receptor antagonist-induced amnesia. In the same experimental conditions BIMU 1 (10 mg kg−1 i.p.; 25 μg/mouse intracerebroventricularly) and BIMU 8 (30 mg kg−1 i.p.; 30 μg per mouse intracerebroventricularly) prevented scopolamine (1 mg kg−1 i.p.) and dicyclomine (2 mg kg−1 i.p.) amnesia and, at the dose of 10 and 30 mg kg−1 i.p. respectively, prevented amnesia induced by exposure to a hypoxic environment. At the highest effective doses, none of the drugs impaired motor coordination, as revealed by the rota rod test, or modified spontaneous motility and inspection activity, as revealed by the hole board and Animex tests. The 5-HT3 antagonist ondansetron (0.1–1 mg kg−1 i.p.) was unable to prevent scopolamine-, 5-HT4 antagonist- and hypoxia-induced amnesia. These results suggest that the modulation of 5-HT4 receptors plays an important role in the regulation of memory processes. On these bases, the 5-HT4 receptor agonists could be useful in the treatment of cognitive deficits although 5-HT4 receptor antagonists may represent pharmacological tools for investigation of new potential antiamnesic drugs.
Footnotes
-
Send reprint requests to: Dr. Carla Ghelardini, Department of Pharmacology, Viale G.B. Morgagni 65, I-50134 Florence, Italy.
-
↵1 This study was supported by grants from MURST.
- Abbreviations:
- i.c.v.
- intracerebroventricular
- BIMU 1
- (endo-N-(8-methyl-8-azabicyclo[3.2.1]-oct-yl)-2,3-dihydro-3-ethyl-2-oxo-1H-benzimidazol-1 carboxamide hydrochloride)
- BIMU 8
- (endo-N-(8-methyl-8-azabicyclo[3.2.1]-oct-3-yl)-2,3-dihydro-(1-methyl)ethyl-2-oxo-1H-benzimidazol-1 carboxamide hydrochloride)
- SDZ 205557
- (2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino) ethyl ester hydrochloride)
- GR 125487
- [1-[2(methylsufonyl)amino]ethyl]-4-piperidinyl] methyl-5-fluoro-2-methoxy-1H-indole-3-carboxylate hydrochloride
- 5-HT
- 5-hydroxytryptamine
- Received July 15, 1997.
- Accepted April 9, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|