Memory retrieval improvement by Ptychopetalum olacoides in young and aging mice

https://doi.org/10.1016/j.jep.2004.07.019Get rights and content

Abstract

Amazonian peoples use traditional remedies prepared with Ptychopetalum olacoides (PO) roots for treating various age-related conditions. This study shows that a single intraperitoneally (i.p.) administration of Ptychopetalum olacoides ethanol extract (POEE, 50 and 100 mg/kg) improved memory retrieval in step-down inhibitory avoidance (P ≤ 0.05 and P ≤ 0.01, test session latency 102 [19.38–300] and 192 [91.3–300] s, respectively versus control 24.7 [12.9–89.6]), without interfering with acquisition or consolidation in adult (2.5-month-old) mice. Comparable results were obtained with POEE given p.o. at 800 and 1000 mg/kg (P ≤ 0.05 and P ≤ 0.01, 52.7 [19.5–297.2] and 85.7 [44.4–260.4] versus control 20.5 [8–92.6]). Moreover, memory amelioration was also observed (P ≤ 0.01) in aging (14 months) mice presenting memory deficit (14.95 [10.8–41]) as compared to adult (2.5 months) mice (57 [15.7–141.2]), with the extract given acutely i.p. 100 mg/kg (300 [133.1–300] versus control 14.95 [10.8–41]) or p.o. 800 mg/kg (28.4 [15.1–84.6] versus control 11.5 [7.8–23.3]). Indeed, aging mice treated with POEE (800 mg/kg, p.o.) performed as well as adult mice. Consistently with its traditional use, the data suggest that POEE facilitates memory retrieval. Although the antioxidant and acetylcholinesterase inhibitory properties previously described for this extract may be of relevance, the molecular mechanism(s) underlying the improvement in memory retrieval here reported merit further scrutiny.

Introduction

Cognitive deficits are often observed in old humans, as well as in various neurological conditions. It has been previously proposed (Kubanis and Zornetzer, 1981) that memory retrieval in the elderly appears to be more impaired than acquisition or storage. Moreover, the first symptoms in Alzheimer's disease include impairment of new information storage or retrieval (Dringenberg, 2000). With the increase of life expectancy and the consequent increase in the number of patients suffering from brain degenerative disorders, the search for products able to reduce or minimize cognitive deficits associated with aging has become even more attractive. Plant species traditionally used in non-western medical systems for enhancing cerebral function, like Gingko biloba and Panax ginseng, have proven to be effective in animal memory tests and useful in cognitively impaired humans (LeBars et al., 1997, Yamaguchi et al., 1997, Curtis-Prior et al., 1999, Zhong et al., 2000).

Ptychopetalum olacoides (PO) Bentham (Olacaceae), known as marapuama, muirapuama or miriantã, is traditionally used in the Brazilian Amazon as a “brain tonic”, specially by those recovering from central nervous systems (CNS) illnesses, by the elderly, and in general to cope with stressful situations; the pharmacological meaning and specific properties of such tonics have yet to be elucidated (Elisabetsky et al., 1992, Elisabetsky and Siqueira, 1998a). Therapeutic outcomes expected from the use of “brain tonics” include facilitating the recovery of cognitive and motor deficits after brain injuries (such as stroke), as well as improvement of cognitive functions, like alertness and memory, in the elderly.

Ptychopetalum olacoides is currently found in dozens of herbal products and multivitamin supplements in several American and European countries (Elisabetsky, 1987, Elisabetsky and Siqueira, 1998b, Paiva et al., 1998), with a diverse range of alleged effects. Previous pharmacological studies demonstrated that an ethanol extract of PO roots potentiated yohimbine-induced lethality, reversed reserpine-induced ptosis and prevented apormophine-induced stereotypy in mice (Siqueira et al., 1998), favorably influenced performance in the forced swimming test (Paiva et al., 1998) and acted as an anxiogenic in the hole board model (da Silva et al., 2001), supporting the hypothesis that Ptychopetalum olacoides has central nervous system effects likely to affect the dopaminergic and noradrenergic systems.

The purpose of this study was to investigate the effects of Ptychopetalum olacoides ethanol extract (POEE) on memory modulation (acquisition, consolidation and retrieval) in adult (2.5-month-old) and aging mice (14-month-old), using the step-down inhibitory avoidance test.

Section snippets

Animals

Experiments were performed using male adult mice, CF1 strain, received from the Fundação Estadual de Produção e Pesquisa em Saúde (FEPPS) immediately after weaning (21 days) or at 14 months of age (35–50 g, aging mice). Animals were maintained in our own animal facility room under controlled environmental conditions (22 ± 1 °C, 12 h-light/12 h-dark cycle, free access to food [Nuvilab CR1] and water); animals were maintained up to 10 weeks of age (25–40 g, adult mice), or in the case of aging mice

Results

Confirming that learning and memory took place with the training paradigm used in this study, there were significant and consistent differences (P < 0.05) between training and test session latencies, in both saline-treated and DMSO-treated adult (2.5 month-old) and aging (14-month-old) groups. No differences in latencies were found in the various groups of training sessions, except for POEE (50 and 100 mg/kg) injected pre-training, when significant (P < 0.01) increases in step-down latencies

Discussion

This study showed that Ptychopetalum olacoides ethanol extract (POEE) improves retrieval in the step-down inhibitory avoidance test in a dose-dependent way, affecting neither memory consolidation nor task acquisition. With reference to the influences of locomotor activity (Zarrindast et al., 1996), although the step-down inhibitory avoidance test is more reliable than other methods for memory assessment, false positives related to diminished motor activity leading to increased test session

Acknowledgements

This study was supported by FAPERGS (grant 98/1610.3), as well as fellowships from CNPq and CAPES. The authors wish to thank Dr. Patricia Shanley for her crucial assistance in collecting plant material. There is a patent request (PI0205432-9; 004142/RS, INPI, Brazil) associated with this study.

References (31)

  • D. Vohora et al.

    Protection from phenytoin-induced cognitive deficit by Bacopa monniera, a reputed Indian nootropic plant

    Journal of Ethnopharmacology

    (2000)
  • Y. Yamaguchi et al.

    Effects of ginsenoside on maze performance and brain choline acetyltransferase activity in scopolamine-treated young rats and aged rats

    European Journal of Pharmacology

    (1997)
  • M. Zarrindast et al.

    Effects of nicotine on memory retrieval in mice

    European Journal of Pharmacology

    (1996)
  • Y. Zhong et al.

    Red ginseng ameliorated placed navigation deficits in young rats with hippocampal lesions and aged rats

    Physiology & Behavior

    (2000)
  • K. Abe et al.

    Effects of saffron extract and its constituent crotin on learning behaviour and long-term potentiation

    Phytotherapy Research

    (2000)
  • Cited by (0)

    View full text