Nimodipine improves spatial working memory and elevates hippocampal acetylcholine in young rats

Levy, Aharon; Kong, Roberto M.; Stillman, Michael J.; Shukitt‐Hale, Barbara; Kadar, Tamar; Rauch, Terry M.; Lieberman, Harris R.

doi:10.1016/0091-3057(91)90164-w

Cited by 68 publications

(31 citation statements)

References 17 publications

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“…Chronic dietary restriction of choline (Nakamura et al 2001) or vitamin A (Cocco et al 2002), and chronic alcohol consumption (Arendt et al 1990;Melis et al 1996) produce correlated deficits in memory and hippocampal ACh. Likewise, many systemic pharmacological treatments that impair memory decrease hippocampal ACh (Hersi et al 1995;Nava et al 2000Nava et al , 2001Mishima et al 2002), whereas systemic drug treatments that enhance memory increase hippocampal ACh (Levy et al 1991;Hersi et al 1995;Scali et al 1997a,b;Bontempi et al 2001;Carey et al 2001;Kopf et al 2001). Similar correlations are observed with intracerebroventricular (i.c.v.)…”

Section: Hippocampal Ach Activity Is Correlated With Memorysupporting

confidence: 66%

Septohippocampal Acetylcholine: Involved in but not Necessary for Learning and Memory?

Parent¹,

Baxter²

2004

Learn. Mem.

175

132

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The neurotransmitter acetylcholine (ACh) has been accorded an important role in supporting learning and memory processes in the hippocampus. Cholinergic activity in the hippocampus is correlated with memory, and restoration of ACh in the hippocampus after disruption of the septohippocampal pathway is sufficient to rescue memory. However, selective ablation of cholinergic septohippocampal projections is largely without effect on hippocampal-dependent learning and memory processes. We consider the evidence underlying each of these statements, and the contradictions they pose for understanding the functional role of hippocampal ACh in memory. We suggest that although hippocampal ACh is involved in memory in the intact brain, it is not necessary for many aspects of hippocampal memory function.The goal of this review is to consider the role of septohippocampal acetylcholine (ACh) in learning and memory processes. The evidence in this regard falls broadly into two different classes. On the one hand, considerable data implicate septohippocampal ACh in memory function. This system is engaged during memory processing, indexed by ACh release or by modification of cholinergic markers, and manipulations that affect memory produce parallel changes in hippocampal cholinergic activity. Furthermore, agents that increase hippocampal cholinergic function are sufficient to reverse memory impairments caused by disruption of the septohippocampal system. However, data from studies of selective lesions of septohippocampal cholinergic neurons with the immunotoxin 192 IgG-saporin call into question the essential role of this system in learning and memory, because these studies generally failed to find severe impairments in memory function. Our goal in this article is to review the data underlying each of these lines of evidence, and to attempt to reconcile these apparently disparate observations.The discrepancy between these lines of evidence might imply that septohippocampal ACh is involved in memory processing, but is not necessary for it to occur. This viewpoint would allow for correlated changes in ACh release and memory, and for the ability of cholinergic agents to reverse memory impairments caused by disruption of septohippocampal function. However, it also would permit memory to proceed relatively normally in the absence of septohippocampal cholinergic input. By describing this viewpoint and its implications for the functional role of hippocampal ACh in memory, we seek to promote the idea that data from lesions are compatible with data from other experimental approaches. Furthermore, we suggest that a convergent approach that incorporates observations from different experimental methods will reveal functional characteristics of hippocampal ACh that would not be apparent from studies using a single strategy.Before discussing the role of this system in cognition, a brief review of its anatomical and neurochemical organization is warranted. The septum is connected to the hippocampus via the fimbria-fornix, which carries projections ...

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Section: Hippocampal Ach Activity Is Correlated With Memorysupporting

confidence: 66%

Septohippocampal Acetylcholine: Involved in but not Necessary for Learning and Memory?

Parent¹,

Baxter²

2004

Learn. Mem.

175

132

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“…These results are in accordance with previous data showing the ability of nimodipine to improve learning in either aged or hypertensive animals. [12][13][14][15][16][17][18][19] Notwithstanding, the present data from middle-aged normotensive WKY and SHR may further suggest that the presence of aging and hypertension produces additive cognitive alterations 2 that can be partially reversed by nimodipine. …”

Section: )mentioning

confidence: 89%

Spontaneously Hypertensive Rats

Meneses

Hong

1998

Hypertension

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Abstract-Spontaneously hypertensive rats (SHR) of 3 to 12 months of age learned and retrieved less information than normotensive Wistar-Kyoto rats (WKY), although no difference was found with animals from 18 and 24 months of age. The combined influence of hypertension and aging had an additive detrimental effect on cognitive functions. Notwithstanding these deficiencies in learning and memory, SHR have seldom been used as a model in the screening of drugs with therapeutic potential for treatment of disorders of cognitive processes. Moreover, the calcium channel blocker nimodipine has beneficial effects on learning in both aged and hypertensive animals and humans. However, no attempt has been made to investigate whether nimodipine can reverse the additive deleterious effects of aging and hypertension in the same subject. We recently reported that deteriorated animals (middle-aged and/or hypertensive) chronically treated with nimodipine (via osmotic minipumps) exhibit higher learning scores. This information indicates that nimodipine can reverse the impairing effects of either aging or hypertension on learning; the presence of the two conditions, however, produces a severe impairment that can be partially reversed by this drug. Therefore, we propose that mature and middle-aged SHR represent a model for the screening of potentially useful drugs in the treatment of learning disorders, probably associated with hypertension and/or aging. Nevertheless, it must be remembered that the SHR is a genetic model and the appearance of neural disturbances could be a parallel genetic phenomenon and not necessarily or exclusively related to hypertension per se. (Hypertension. 1998;31:968-972.)Key Words: rats, inbred SHR Ⅲ learning Ⅲ memory Ⅲ aging Ⅲ pharmacology Ⅲ models A great expansion of experimental research began with the development of rat strains with genetically inherited hypertension. The SHR offers specific and uniform genetic predisposition, 1 thus allowing the study of the causes, mechanisms, and pathology of hypertension, as well as its behavioral consequences, and the comparison of the efficacy of proposed therapeutic interventions in relation to existing clinical treatments. Moreover, central neurohormonal mechanisms constitute the dominating trigger influence in SHR 1 and provide a model of hypertension that allows the study of the combined influence of both aging and hypertension on cognitive and physical functions on different developmental stages.2,3 Notwithstanding, the SHR is a genetic model, and the appearance of neural disturbances could be a parallel genetic phenomenon and not necessarily or exclusively related to the elevated blood pressure per se. Normal aging also produces a slow decline in neuron population, tissue distensibility, basal metabolic rate, and oxygen consumption, thus affecting cardiovascular performance. The aim of the present work was to present evidence obtained in our laboratory supporting the idea that the SHR is a suitable behavioral model to test drugs with potential therapeutic us...

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“…Additionally, these memoryenhancing effects of DCCCA might be mediated by non-catecholamine systems. For instance, rises in acetylcholine induced by the DCCCA, nimodipine, have been associated with enhancements of spatial memory in rats (Levy et al 1991). Similarly, when rhesus monkeys with calcium imbalance are treated with nimodipine there is a significant improvement in short-term memory (LeVere and LeVere 1994).…”

Section: Discussionmentioning

confidence: 99%

Effects of Isradipine, a Dihydropyridine-Class Calcium Channel Antagonist, on D-Methamphetamine-Induced Cognitive and Physiological Changes in Humans

Johnson

Ait-Daoud

Wells

2000

Neuropsychopharmacology

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Nimodipine improves spatial working memory and elevates hippocampal acetylcholine in young rats

Cited by 68 publications

References 17 publications

Septohippocampal Acetylcholine: Involved in but not Necessary for Learning and Memory?

Septohippocampal Acetylcholine: Involved in but not Necessary for Learning and Memory?

Spontaneously Hypertensive Rats

Effects of Isradipine, a Dihydropyridine-Class Calcium Channel Antagonist, on D-Methamphetamine-Induced Cognitive and Physiological Changes in Humans

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