Conceptualizing and measuring potentially inappropriate drug therapy.

WHAT IS KNOWN AND OBJECTIVE: Elderly people are the principal consumers of prescription drugs. The more the medication used by the patient, the greater the likelihood there is of the patient being subjected to potentially inappropriate drug therapy (PIDT). PIDT has been measured in the literature with both implicit and explicit tools. The purpose of this review was to assess the use of tools to detect PIDT in various studies and to determine which terms are used to refer to PIDT in practice. METHODS: A systematic review was conducted according to the following steps: the first was identification. In this step, studies were selected from different combinations of the descriptors 'aged', 'elderly', 'inappropriate prescribing' and 'drug utilization' in three different languages, using the Embase, Medline, Scielo, Scopus and Web of Science databases. Second, the papers that satisfied the inclusion criteria for data extraction were carefully examined by three evaluators to determine the tools used and terms that referred to PIDT. RESULTS AND DISCUSSION: From the combinations of keywords, 8610 articles were found. At the end of the selection process, 119 of the articles complied with the specified criteria. The degree of agreement among evaluators was moderate for the study titles (κ1  = 0·479) and substantial for abstracts (κ2  = 0·647). With respect to the PIDT evaluation criteria used by the studies, 27·7% used two criteria. Of the 27 evaluation criteria identified, the Beers criteria were used by 82·3% of the studies. More than 50 different terms to identify PIDT were found in the literature. WHAT IS NEW AND CONCLUSION: This review is the first study to conceptualize and discuss terms that refer to PIDT. At present, there is no consensus regarding terms used to refer to PIDT, with over 50 different terms currently in use. This review shows an increase in the number of articles aimed at evaluating PIDT using implicit and explicit tools.

Experimental hypothyroidism during pregnancy affects nociception and locomotor performance of offspring in rats.

BACKGROUND: Thyroid hormones (THs) play a crucial role in the development of several organic systems. An adequate support of maternal THs may be required to ensure a normal nociceptive function of offspring into adulthood. We investigated the impact of experimental gestational hypothyroidism (EGH) on nociceptive threshold and motor performance in the offspring at different post-natal days (PND) in both male and female rats. METHODS: EGH was induced by the administration of 0.02% methimazole (MMI) in the drinking water from the ninth day of gestation until birth. The offspring from MMI-treated dams (OMTDs) or from water-treated dams (OWTDs) were assessed for thermal and mechanical nociception using the tail-flick test and von Frey filaments, respectively. Both rota-rod and grip strength were used to assess motor function. RESULTS: OMTD had reduced thermal (p<0.05) but not mechanical threshold at all studied ages (60 and 120 PND). Sixty-day-old OMTD presented reduced latency to the tail-flick test (p=0.01). Grip strength in 120-day-old OMTD was reduced (p<0.01). However, only male OMTD presented a lower locomotor performance on the rota-rod test when analysed on the 60th PND (p<0.01). CONCLUSIONS: EGH promotes hypersensitivity to noxious thermal but not mechanical stimulus. Moreover, motor force is similarly reduced in male and female OMTDs, whereas motor performance is reduced only in mature male OMTD, suggesting the presence of a protective factor in females.

Sida cordifolia leaf extract reduces the orofacial nociceptive response in mice.

In this study, we describe the antinociceptive activity of the ethanol extract (EE), chloroform (CF) and methanol (MF) fractions obtained from Sida cordifolia, popularly known in Brazil as "malva branca" or "malva branca sedosa". Leaves of S. cordifolia were used to produce the crude ethanol extract and after CF and MF. Experiments were conducted on Swiss mice using the glutamate and formalin-induced orofacial nociception. In the formalin test, all doses of EE, CF and MF significantly reduced the orofacial nociception in the first (p < 0.001) and second phase (p < 0.001), which was also naloxone-sensitive. In the glutamate-induced nociception test, only CF and MF significantly reduced the orofacial nociceptive behavior with inhibition percentage values of 48.1% (100 mg/kg, CF), 56.1% (200 mg/kg, CF), 66.4% (400 mg/kg, CF), 48.2 (200 mg/kg, MF) and 60.1 (400 mg/kg, MF). Furthermore, treatment of the animals with EE, CF and MF was not able to promote motor activity changes. These data demonstrate that S. cordifolia has a pronounced antinociceptive activity on orofacial nociception. However, pharmacological and chemical studies are necessary in order to characterize the responsible mechanisms for this antinociceptive action and also to identify other bioactive compounds present in S. cordifolia.

Analysis of the quality of prescriptions at a cardiovascular ward in Brazil: a pilot study.

AIM OF STUDY: To analyze the quality of prescriptions in a hospital in Brazil. METHODS: A cross-sectional pilot study of the quality of prescriptions of adult patients admitted at the cardiovascular ward. Data were collected with the help of a structured form developed by the researchers based on related literature, with items about medications and completeness of prescriptions. The form was divided into four categories of prescription quality indicators: prescription type, legibility and readability of handwriting, and completeness. MAIN OUTCOME MEASURES 100 patients participated in the study, with ages between 20 and 94 years (mean of 67.12 ± 16.6 years), We analyzed 5,030 on 496 prescriptions for 100 patients. Of 11% the handwriting was considered to be less legible and 17% considered illegible. In terms of readability, a high incidence of medications were prescribed by their brand names (89%), and 13,707 abbreviations (mean of 27.6 per prescription) were used mainly to refer to the route of administration (31%), concentration (27%), and indications for use (20%). In relation to completeness, 471 (95%) prescriptions were considered incomplete, mainly medication data. CONCLUSION: The quality indicators used in this study revealed a high rate of prescription problems and errors.

Evaluation of the analgesic and anti-inflammatory effects of the essential oil of Lippia gracilis leaves.

AIM OF THE STUDY: The aim of the present study is to investigate the antinociceptive, anti-inflammatory, and antioxidant activities of essential oil (EO) of Lippia gracilis Schauer (Verbenaceae) leaves to support the medicinal uses claimed by folklore practitioners in the caatinga region (semi-arid) of Northeastern Brazil. MATERIALS AND METHODS: The chemical composition and antinociceptive and anti-inflammatory activities of the EO of Lippia gracilis leaves (50-200 mg/kg) were investigated. Antinociceptive activity of the EO was evaluated by writhing test. Anti-inflammatory activity of the EO was evaluated using paw oedema and peritonitis methods. RESULTS: Oral treatment with the EO of Lippia gracilis leaves elicited inhibitory activity on acetic acid effect at 50, 100, and 200 mg/kg (30.33+/-2.36, 25.20+/-1.48, and 21.00+/-1.54 abdominal writhes, respectively, P<0.05), as compared with the control group (36.73+/-1.92 writhes). The compound acetylsalicylic acid (ASA, 300 mg/kg) inhibited the acetic acid-induced writhing (12.67+/-0.50 abdominal writhes, P<0.001). Carrageenan-induced oedema formation was reduced with the EO of Lippia gracilis leaves at 200 mg/kg (0.72+/-0.06 mL h, P<0.001) and by the reference compound ASA (300 mg/kg, 0.85+/-0.04 mL h, P<0.001), as compared with the control group (1.76+/-0.06 mL h). Leukocyte migration into the peritoneal cavity induced by carrageenan was reduced with the EO of Lippia gracilis leaves at 50, 100, and 200 mg/kg (13.81+/-0.61, 11.77+/-0.91, and 10.30+/-0.60 leukocytes x 10(6)/mL, respectively, P<0.01), and by the compound dexamethasone (2 mg/kg, 5.34+/-0.33 leukocytes x 10(6)/mL, P<0.001), as compared with the control group (16.71+/-0.54 leukocytes x 10(6)/mL). The analyses of the essential oil allowed the identification of Lippia gracilis as a thymol-p-cymene chemotype (32.68% and 17.82%, respectively). CONCLUSIONS: The EO of Lippia gracilis leaves shows antinociceptive and anti-inflammatory activities.

Antinociceptive and anti-inflammatory activities of Bowdichia virgilioides (sucupira).

ETHNOPHARMACOLOGICAL RELEVANCE: Bowdichia virgilioides Kunth (Leguminosae Papilonoideae) is a plant with anti-inflammatory activity used in folk medicine. The importance of this plant promoted its inclusion in Brazilian Pharmacopoeia. AIM OF THE STUDY: In order to evaluate the actions of this plant, studies were performed on antinociceptive and anti-inflammatory activities. MATERIALS AND METHODS: The aqueous extracts (AE) of Bowdichia virgilioides inner bark and leaves were used at 100, 200, and 400mg/kg. Antinociceptive activity of plant extract was evaluated by writhing, hot-plate and formalin tests. Anti-inflammatory activity was evaluated using paw oedema and peritonitis methods. RESULTS: Oral treatment with the AE of inner bark or leaves elicited inhibitory activity (P<0.01) on acetic acid effect at 200 and 400mg/kg, and reduced the formalin effect at the second-phase (200 and 400mg/kg, P<0.01), however it did not elicit any inhibitory effect on hot-plate test. The indomethacin inhibited the acetic acid-induced writhing and the formalin effect at the second-phase (P<0.001), and the morphine reduced the both phases of formalin test (P<0.001). Carrageenan-induced oedema formation and neutrophil migration into the peritoneal cavity were reduced with the AE of inner bark or leaves at 100, 200, and 400mg/kg (P<0.05), and by the reference compounds aspirin (P<0.001) and dexamethasone (P<0.001), respectively. CONCLUSIONS: The AE of Bowdichia virgilioides shows antinociceptive and anti-inflammatory activities, supporting the folkloric usage of the plant to treat various inflammatory diseases.

Antinociceptive activity of the volatile oils of Hyptis pectinata L. Poit. (Lamiaceae) genotypes.

Hyptis pectinata L. Poit (Lamiaceae) is known popularly in Brazil as "sambacaita" or "canudinho" and is used in the treatment of inflammations, bacterial infections and ache. The antinociceptive activity of the volatile oils of six genotypes, at doses of 100, 200 and 400mg/kg body wt., were investigated using abdominal writhe models induced by acetic acid and hot plate tests. The volatile oils of all the genotypes are composed mainly of sesquiterpenoids. All the genotypes showed antinociceptive effects in both models used; the SAM002 genotype showed the major inhibitory effect at dose of 100mg/kg body wt. These results suggest that the volatile oil of H. pectinata has peripheral (writhe reduction) and central (time delay of thermal reaction) effects. These observations indicate that H. pectinata may be useful as an analgesic drug.

Phythochemical screening and anticonvulsant activity of Cymbopogon winterianus Jowitt (Poaceae) leaf essential oil in rodents.

Cymbopogon winterianus (Poaceae) is used for its analgesic, anxiolytic and anticonvulsant properties in Brazilian folk medicine. This report aimed to perform phythochemical screening and to investigate the possible anticonvulsant effects of the essential oil (EO) from fresh leaves of C. winterianus in different models of epilepsy. The phytochemical analysis of EO showed presence of geraniol (40.06%), citronellal (27.44%) and citronellol (10.45%) as the main compounds. A behavioral screening demonstrated that EO (100, 200 and 400mg/kg; ip) caused depressant activity on CNS. When administered concurrently, EO (200 and 400mg/kg, ip) significantly reduced the number of animals that exhibited PTZ- and PIC-induced seizures in 50% of the experimental animals (p<0.05). Additionally, EO (100, 200 and 400mg/kg, ip) significantly increased (p<0.05) the latencies of clonic seizures induced by STR. Our results demonstrated a possible activity anticonvulsant of the EO.

Cardiovascular effects of Hyptis fruticosa essential oil in rats.

In non-anesthetized normotensive rats, Hyptis fruticosa essential oil (HFEO, 5, 10, 20 and 40 mg/kg; i.v.) induced hypotension associated with tachycardia. In intact and isolated rings of rat superior mesenteric artery (control), HFEO (1-1000 microg/ml, n=6, cumulatively) induced concentration-dependent relaxations of tonus induced by 10 microM phenylephrine (Phe) (pD(2)=2.6+/-0.27; E(max)=64+/-8.3%). In denuded endothelium pre-contracted rings with Phe or K(+)-depolarizing solution (80 mM), the concentration-response curves to HFEO were not shifted (pD(2)=2.3+/-0.25 and 2.3+/-0.28, respectively), but their maximal responses were significantly (P<0.05 vs control) increased (E(max)=122.3+/-18.2% and 92+/-3.6%, respectively). HFEO was also capable of antagonizing the concentration-response curves to CaCl(2) (3 microM-30 mM) in a dose-dependent manner.

Antifungal activity of Brazilian medicinal plants involved in popular treatment of mycoses.

A survey of medicinal plants used to treat common mycoses was done in the Curituba district, Sergipe State, Brazil. One hundred inhabitants were interviewed by health agents and traditional healers. Four different plants were the most cited (more than 50% of the citations): Ziziphus joazeiro, Caesalpinia pyramidalis, Bumelia sartorum and Hymenea courbaril. The aqueous extracts obtained following traditional methods and using different parts of these plants, were submitted to drop agar diffusion tests for primary antimicrobial screening. Only the water infusion extract of Ziziphus joazeiro and Caesalpinea pyramidalis presented a significant antifungal activity against Trichophyton rubrum, Candida guilliermondii, Candida albicans, Cryptococcus neoformans and Fonsecaea pedrosoi, when compared to the antifungal agent amphotericin B. The minimal inhibitory concentration (MIC) of the bioactive extracts was evaluated by the microdilution method. Best activity with a MIC of 6.5 microg/ml for both extracts was observed against Trichophyton rubrum and Candida guilliermondii. Ziziphus joazeiro and Caesalpinea pyramidalis extracts presented also low acute toxicity in murine models. The present study validates the folk use of these plant extracts and indicates that they can be effective potential candidates for the development of new strategies to treat fungal infections.

Endothelium-derived factors and k+ channels are involved in the vasorelaxation induced by Sida cordifolia L. in the rat superior mesenteric artery.

The vasorelaxantion of the aqueous fraction of the hydroalcoholic extract of the Sida cordifolia leaves (AFSC) was evaluated in this work. In rat superior mesenteric artery, AFSC (3-1000 microg/mL) induced relaxation of phenylephrine-induced contractions. This effect was significantly attenuated after removal of the endothelium, after atropine (1 microM), L-NAME (100 microM), indomethacin (10 microM), high K+ (20 mM), tetraethylammonium (1 microM), a K(Ca) blocker, apamin (1 microM), a SK(Ca) blocker and ChTX (0.1 microM), a BK(Ca) blocker, however, it was not affected after glibenclamide (10 microM), an KATP blocker, and 4-aminopyridine (1 microM), a Kv blocker. ChTX (0.1 microM) was able to induce an additional inhibition of the vasorelaxation induced by AFSC in the presence of L-NAME plus indomethacin. The vasorelaxation induced by AFSC in the presence of L-NAME plus indomethacin plus ChTX was not different from that induced by AFSC in rings without endothelium. In conclusion, the results show that endothelium-derived factors (mainly NO, PGI2) and K+ channels (BK(Ca) and SK(Ca)) play a crucial role in the vasorelaxation induced by AFSC in the rat superior mesenteric artery.

Lead effects on non-adrenergic non-cholinergic relaxations in the rat gastric fundus.

The effect of lead exposure on non-adrenergic non-cholinergic (NANC) relaxations in rat gastric fundus was evaluated in this work. Wistar rats were divided into four groups: The control group received tap water and the three other received 0.008% of lead acetate in their drinking water for 15, 30 and 120 days. NANC relaxations induced by electrical field stimulation (0.5-8 Hz, 1 ms, 60 V) of gastric fundus strips was inhibited in all groups treated with lead. The strips from groups, control and 120 days of lead treatment (LEAD 120), were incubated with L-NOARG (100 microM). The presence of this blocker did not produce any additional inhibition. Sodium nitroprusside (10(-10)-10(-6) M) and 8-Br-GMPc (3 x 10(-8)-3 x 10(-4) M) produced dose-dependent relaxations in strips of both groups control and LEAD 120, however, in the LEAD 120, the potencies were significantly reduced from 7.32 +/- 0.05 to 6.40 +/- 0.09 (n = 5) and 4.26 +/- 0.06 to 3.69 +/- 0.05 (n = 5), respectively. Our data suggest that the chronic exposure to lead inhibits NANC relaxations probably by modulating NO release from NANC nerves and/or by interacting with intracellular transducer mechanisms in rat gastric fundus.

Morphological, agronomical and pharmacological characterization of Hyptis pectinata (L.) Poit germplasm

Several species of the genus Hyptis have presented medicinal characteristics and are frequently indicated to treat gastro intestinal infections, gramps and pain, as well as for skin infections. Three harvests were carried out using six H. pectinata accessions, and the following characteristics were evaluated: plant height, canopy diameter, leave length (L) and width (W), L/W relation and dry weight of leaves and stem. The accession SAM006 have presented highest leave dry matter yield when the three harvests were summed. The aqueous leaf extracts of the same six H. pectinata accessions were tested for anti-edematogenic effect using the carrageenin-induced rat paw edema at doses of 200, 400 and 600 mg/kg. The extracts administered orally had a significant anti-edematogenic effect. The dose of 200 mg/kg of accessions SAM004 and SAM005 had a stronger effect reducing the edema by 19.6 percent and 15.4 percent, respectively. Similar results were obtained using higher dosages of the aqueous extract of the accessions SAM002, SAM003 and SAM006. It can be concluded that the accessions SAM004, SAM005 and SAM006 are promising genotypes for a plant breeding program that aims the development of a cultivar with highest leave yielding and anti-edematogenic effect.

Effect of the aqueous extract of Hyptis pectinata on liver mitochondrial respiration.

Some studies have indicated that mitochondria may be the target organelle of plants. We therefore decided to assess the effects of the aqueous extract of Hyptis pectinata leaves on liver mitochondrial respiratory function in vitro. Eight rat livers were subjected to isolation of mitochondria by differential centrifugation. In an adequate medium, the plant extract was added at different concentrations. The analyzed data were: state 3, state 4 and respiratory control ratio (RCR). H. pectinata extract caused a statistically significant decrease in state 3 (at 0.05, 0.1 and 0.2 mg/mg protein) and RCR (at 0.05, 0.1 and 0.2 mg/mg protein). Respiratory state 4 was not altered by the increasing concentrations. In conclusion, the aqueous extract of H. pectinata leaves may not injure the mitochondrial inner membrane but decreases significantly the oxidative phosphorylation.

CNS pharmacological effects of the hydroalcoholic extract of Sida cordifolia L. leaves.

Sida cordifolia L. (Malvaceae), known as "malva branca", is a plant used in the popular medicine for the treatment stomatits, of asthma and nasal congestion. This work researched the acute toxicity of Sida cordifolia and its action on the central nervous system (CNS) because no data in the literature have been found about of pharmacological activity of this plant in the CNS. The hydroalcoholic extract of Sida cordifolia leaves (HESc) was used and the psychopharmacology approach began with the determination of LD(50), where a low toxicity was observed in mice. Depressive activity on CNS was demonstrated by several alterations in mice's behavior in the pharmacological screening. In the motility test, the HESc showed significant reduction of spontaneous activity at a dose of 1000 mg/kg (i.p.) at 30 and 60 min. The same form the HESc also decreased the ambulation and rearing in open-field test at 30, 60 and 120 min at a dose of 1000 mg/kg (i.p.).

Central nervous system effects of the crude extract of Erythrina velutina on rodents.

The aqueous extract (AE) of Erythrina velutina prolonged the sleep duration induced by sodium pentobarbital (control: 6.4 +/- 1.2 min; extract 10 mg/kg, 47.1 +/- 3.9 min; extract 100 mg/kg, 109.4 +/- 7.2 min; F = 243, P < 0.001). In the open field, the extract at the doses of 10 and 50 mg/kg did not changed the number of crossings, rearings nor groomings. On the other hand, at the dose of 200 mg/kg it reduced the number of crossings (q = 6.25, P < 0.05) and groomings (q = 3.91, P < 0.05). When exposed during three consecutive days to the open field, the control animals showed habituation for crossings (F = 17.56, P < 0.001) and rearings (F = 14.01, P < 0.001). The same was not true for animals treated with 10 mg/kg of the extract (crossings: F = 3.59, P > 0.05; rearings: F = 3.62, P > 0.05). At the same dose, the extract blocked the acquisition of foot shock memory (P = 0.9219) when compared to the control values (P = 0.0078). Our data showed that the crude extract of Erythrina velutina at lower doses interferes with mnemonic process for different tasks, while at higher doses, the sedative and neuromuscular blocking actions are the main effects.

Antinociceptive and antiedematogenic properties and acute toxicity of Tabebuia avellanedae Lor. ex Griseb. inner bark aqueous extract.

BACKGROUND: Tabebuia avellanedae is a tree from the Bignoniaceae family. Commonly know as "pau d'arco" in Brazil, its inner bark is used as analgesic, anti-inflammatory, antineoplasic and diuretic at the Brazilian northeast. A validation of the plant usage has not been previously performed. RESULTS: Antinociceptive and antiedematogenic effects of Tabebuia avellanedae Lor. ex Griseb. inner bark were measured by nociceptive experimental models in mice. A rat paw edema test induced by carrageenan (1%) was also performed in rats to access the plant's antiedematogenic effect. The inner bark aqueous extract, administered via oral in three different concentration, namely 100, 200 and 400 mg/Kg, reduced the nociception produced by acetic acid (0.6% in water, i.p.) by 49.9%, 63.7% and 43.8%, respectively. The aqueous extract (200 and 400 mg/Kg, p.o.) reduced formalin (1%) effects only at the second phase of the experiment by 49.3% and 53.7%, respectively. Naloxone (5 mg/Kg, i.p.) was not able to revert the extract effect, however caffeine (10 mg/Kg, i.p.) reverted its effect by 19.8% at the second phase of the formalin test. The aqueous extract (200 mg/Kg, p.o.) inhibited edema by 12.9% when we used the rat paw edema model. The acute toxicity was low in mice. CONCLUSION: The T. avellanedae inner bark aqueous extract presented antinociceptive and antiedematogenic activities at the used models, with a possible antinociceptive effect associated to the adenosine system.

Antinociceptive and antiedematogenic effects of the aqueous extract of Hyptis pectinata leaves in experimental animals.

The aqueous leaf extract of Hyptis pectinata (L.) Poit (Lamiaceae), popularly known in Brazil as "sambaicatá" or "canudinho", was tested for its antinociceptive effects using the abdominal writhing, hot plate and formalin test models, and for its aniedematogenic effects using the carrageenin and arachidonic acid-induced rat paw edema. The aqueous extract of Hyptis pectinata administered orally at doses of 100, 200 and 400 mg/kg had a significant antinociceptive effect in the test of acetic acid-induced abdominal writhing, with 43, 51 and 54% reduction of writhes, respectively, compared to the control. An increase in hot-plate latency of 47 and 37.5% was also observed in animals receiving doses of 200 and 400 mg/kg, p.o. when placed on a hot plate. In the formalin test, doses of 200 and 400 mg/kg, p.o. had no significant effect during the first phase of the test (0-5 min), while the dose of 200 mg/kg, p.o. reduced the nociceptive effect by 70% during the second phase (20-25 min). At the dose of 600 mg/kg, p.o., the aqueous extract inhibited carrageenin-induced rat paw edema by 34.1%, and the dose of 300 mg/kg administered intraperitoneally inhibited the rat paw edema induced by subplantar injection of arachidonic acid by 32.8%. These results suggest that the aqueous extract from the Hyptis pectinata leaves produces antiedematogenic and antinociceptive effects. The antinocipetion observed with the hot-plate test probably involves the participation of the opioid system.

Differential effects of lead and zinc on inhibitory avoidance learning in mice.

We studied the effects of chronic intoxication with the heavy metals lead (Pb2+) and zinc (Zn2+) on memory formation in mice. Animals were intoxicated through drinking water during the pre- and postnatal periods and then tested in the step-through inhibitory avoidance memory task. Chronic postnatal intoxication with Pb2+ did not change the step-through latency values recorded during the 4 weeks of the test (ANOVA, P>0.05). In contrast, mice intoxicated during the prenatal period showed significantly reduced latency values when compared to the control group (day 1: q = 4.62, P<0.05; day 7: q = 4.42, P<0.05; day 14: q = 5.65, P<0.05; day 21: q = 3.96, P<0.05, and day 28: q = 6.09, P<0.05). Although chronic postnatal intoxication with Zn2+ did not alter a memory retention test performed 24 h after training, we noticed a gradual decrease in latency at subsequent 4-week intervals (F = 3.07, P<0.05), an effect that was not observed in the control or in the Pb2+-treated groups. These results suggest an impairment of memory formation by Pb2+ when the animals are exposed during the critical period of neurogenesis, while Zn2+ appears to facilitate learning extinction.

Differential effects of lead and zinc on inhibitory avoidance learning in mice

We studied the effects of chronic intoxication with the heavy metals lead (Pb2+) and zinc (Zn2+) on memory formation in mice. Animals were intoxicated through drinking water during the pre- and postnatal periods and then tested in the step-through inhibitory avoidance memory task. Chronic postnatal intoxication with Pb2+ did not change the step-through latency values recorded during the 4 weeks of the test (ANOVA, P>0.05). In contrast, mice intoxicated during the prenatal period showed significantly reduced latency values when compared to the control group (day 1: q = 4.62, P<0.05; day 7: q = 4.42, P<0.05; day 14: q = 5.65, P<0.05; day 21: q = 3.96, P<0.05, and day 28: q = 6.09, P<0.05). Although chronic postnatal intoxication with Zn2+ did not alter a memory retention test performed 24 h after training, we noticed a gradual decrease in latency at subsequent 4-week intervals (F = 3.07, P<0.05), an effect that was not observed in the control or in the Pb2+-treated groups. These results suggest an impairment of memory formation by Pb2+ when the animals are exposed during the critical period of neurogenesis, while Zn2+ appears to facilitate learning extinction