Nimodipine prevents scopolamine-induced impairments in object recognition

Abstract

The effects of acute administration of the dihydropyridine calcium channel antagonist, nimodipine, were studied on the actions of scopolamine in the object recognition test. Scopolamine at 0.125 mg/kg decreased the difference in the time spent exploring novel and familiar objects when given either 15 min before, or immediately after, exposure to objects. Administration of nimodipine at 10 mg/kg, or 1 mg/kg, at the same time as the scopolamine completely prevented the deleterious effects on memory in this task. This effect was seen when nimodipine and/or scopolamine were given prior to the object exposure and also when the drugs were given after the experience of seeing the objects. Nimodipine had no effects on performance when given in the absence of scopolamine. This lack of change in total time spent exploring the objects indicated that the effects of scopolamine and nimodipine were not due to changes in motor coordination or alertness. The results are discussed in the light of the role of cholinergic transmission in memory and the known actions of dihydropyridines on brain function.

Differential Effects of Scopolamine on Memory Processes in the Object Recognition Test and the Morris Water Maze Test in Mice

“…reported that the familiarity discrimination was impaired by scopolamine administration before acquisition but not after acquisition. It was also reported that scopolamine decreased the difference in the time spent exploring novel and familiar objects either by administration 15 min before or by administration immediately after exposure to objects, suggesting scopolamine deteriorates acquisition and consolidation phases (Norman et al, 2002). Consistent with the previous report, we also observed that scopolamine impaired those memory phases, although the doses and the time points used are slightly different.…”

A specific role for septohippocampal acetylcholine in memory?

“…Scopolamine is so well-established as an amnestic drug that it is often used as a model to induce a memory deficit which then a potential promnestic agent may redress (e.g., Norman, Brooks, Hennebry, Eacott, & Little, 2002). In rats, systemic or central administration of this drug impairs performance in several hippocampus-dependent tasks including the Morris water maze (Herrera-Morales, Mar, Serrano, & Bermudez-Rattoni, 2007; Janas et al, 2005; von Linstow Roloff, Harbaran, Micheau, Platt, & Riedel, 2007), the radial arm maze (Masuoka, Fujii, & Kamei, 2006; Mishima et al, 2000), spatial alternation in a T-maze (Givens & Olton, 1995), contextual fear conditioning (Anagnostaras, Maren, Sage, Goodrich, & Fanselow, 1999; Wallenstein & Vago, 2001) and spatial discrimination task (Carli, Luschi, & Samanin, 1997).…”

Antagonism of L-type Cav channels with nifedipine differentially affects performance of wildtype and NK1R−/− mice in the 5-Choice Serial Reaction-Time Task

“…The majority of these NK1R-expressing interneurons are cholinergic (Gerfen, 1991), but some are GABAergic (NPY/somatostatin (SOM)/NOS-expressing) (Kawaguchi et al, 1995;Li et al, 2002). Nifedipine-sensitive (L-type) channels are expressed by striatal neurons where they are involved in corticostriatal plasticity (Norman et al, 2002;Bonsi et al, 2004). These channels have been linked to periodic burstfiring of cholinergic interneurons (Goldberg and Wilson, 2005;Goldberg et al, 2009), and nifedipine attenuates acetylcholine efflux (Sanz et al, 2000).…”