Elsevier

Neuropharmacology

Volume 36, Issues 4–5, April–May 1997, Pages 697-706
Neuropharmacology

BIMU1 Increases Associative Memory in Rats by Activating 5-HT4 Receptors

https://doi.org/10.1016/S0028-3908(97)00058-0Get rights and content

Abstract

Olfactory association learning was used to investigate the involvement of 5-HT4 receptors in learning and long-term memory. The behavioral role of the 5-HT4 receptors was studied by using BIMU1 (3-ethyl-2,3-dihydro-N-[endo-8-methyl-8-azabicyclo(3.2.1)oct-3-yl]-2-oxo-1H-benzimidazole-1-carboxamide, hydrochloride (Boehringer Ingelheim, Italy); a mixed 5-HT4 agonist/5-HT3 antagonist, and GR125487 (1-[2-[methyl sulphonyl)-amino]ethyl]-4-piperidinyl-methyl 5-fluoro-2-methoxy-1H-indole-3-carboxylate; Glaxo Group Research, Hertfordshire, U.K.), a specific 5-HT4 antagonist. The intraperitoneal injections of BIMU1 at 1, 5, and 10 mg/kg were followed by an substantial improvement (>15% in percentage of correct responses at the dose of 10 mg/kg) in associative memory. Difficulty rapidly reversing behavioral responses to previously learned association, 1 month later indicated that the BIMU1 effect at 10 mg/kg was not transient, but correlated to long-term memory. The effects of BIMU1 are most likely to be mediated by 5-HT4 receptors since they were blocked by GR125487 at 10 mg/kg. These data suggest that activation of 5-HT4 receptors may modulate cognitive processes like learning and memory. © 1997 Elsevier Science Ltd.

Section snippets

Animals

Male adult Sprague-Dawley rats (300–350 g) from the IFFA CREDO Company (L'arbresle, France) were used in all experiments. They were individually housed and kept on a 24hr light-dark cycle (lights on at 7:00 a.m. and off at 7:00 p.m.) in a room held at a constant temperature (22°C). Each animal was handled (10 min) every day for 3 days and then deprived of water for 48 hr before training.

Apparatus and training procedure

The olfactory training apparatus was a rectangular box made of wire mesh (30 × 30 × 50 cm). A conical odor

Experiment 1

The four groups improved their performance across sessions, reaching a correct response score of 80% or better on session 5 (see Table 1).

A MANOVA indicated a group difference across the five sessions for the percentage of correct responses [F(3,24) = 3.79, p = 0.024]. Indeed, following the injection on session 3, the three BIMU1 groups improved their performance compared to the saline groups. The improvement in the correct response rate was not as great for the BIMU1 1 and 5 groups as for the

DISCUSSION

The present results show that BIMU1 is a potential memory facilitating agent. Following the injection of BIMU1 (10 mg/kg), a highly significant improvement in performance (higher correct response rate) was apparent in comparison to the saline treated (CONTROL) animals, assessed using an olfactory association learning test. A similar but more modest effect was observed with BIMU1 (1 and 5 mg/kg). This improvement was partially maintained during the fourth and the fifth sessions. The latency

Acknowledgements

This work was supported by the CNRS. The authors are grateful for the expert secretarial assistance of Michelle Bauget and for the technical assistance of Alain Bouquerel.

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