Dissociation of the effects of ethanol on memory, anxiety, and motor behavior in mice tested in the plus-maze discriminative avoidance task.

RATIONALE: Several studies have shown the amnestic effects of ethanol (ETOH). However, while memory tasks in rodents can be markedly influenced by anxiety-like behavior and motor function, ETOH induces anxiolysis and different effects on locomotion, depending on the dose. OBJECTIVE: Verify the effects of ETOH in mice tested in the plus-maze discriminative avoidance task (PMDAT) concomitantly evaluating memory, anxiety-like behavior, and motor behavior. METHODS: ETOH acutely or repeatedly treated mice were submitted to the training session in a modified elevated plus-maze with two open and two enclosed arms, aversive stimuli in one of the enclosed arms, and tested 24 h later without aversive stimuli. Learning/memory, locomotion, and anxiety-related behavior were evaluated by aversive arm exploration, number of entries in all the arms and open arms exploration, respectively. RESULTS: Acute ETOH: (1) either increased (1.2-1.8 g/kg) or decreased (3.0 g/kg) locomotion; (2) decreased anxiety levels (1.2-3.0 g/kg); and (3) induced learning deficits (1.2-3.0 g/kg) and memory deficits (0.3-3.0 g/kg). After repeated treatment, sensitization and tolerance to hyperlocomotion and anxiolysis induced by 1.8 g/kg ETOH were observed, respectively, and tolerance to the amnestic effect of 0.6 (but not 1.8) g/kg ETOH occurred. CONCLUSION: Neither the anxiolytic nor the locomotor effects of ETOH seem to be related to its amnestic effect in the PMDAT. Additionally, data give support to the effectiveness of the PMDAT in simultaneously evaluating learning, memory, anxiety-like behavior, and motor activity by different parameters. Possible relationships between the behavioral alterations found are discussed.

Drug-induced home cage conspecifics' behavior can potentiate behavioral sensitization in mice.

The effect of home cage conspecifics' behavior on locomotor sensitization to amphetamine (AMP) or ethanol (ETOH) were investigated. Female mice were repeatedly treated with saline or AMP (2.0 mg/kg for 13 days--Experiment 1) or saline or ETOH (1.8 g/kg for 21 days--Experiment 2) in home cages where all the animals had the same treatment (homogeneous home cages--HOM-HC) or in home cages where half of the animals were drug-treated and half of them were saline-treated (heterogeneous home cages--HET-HC). Behavioral sensitization was evaluated by the quantification of open-field locomotor activity after AMP or ETOH challenge injection, respectively. In both experiments, behavioral sensitization was potentiated in HOM-HC maintained animals. These results suggest that the behavioral sensitization phenomenon can be modified by home cage conspecifics' behavior.

Important role of striatal catalase in aging- and reserpine-induced oral dyskinesia.

Tardive dyskinesia, the most serious iatrogenic movement disorder, has been tentatively associated with nigrostriatal dopaminergic supersensitivity and with oxidative stress. It is also suggested that long-term neuroleptic treatment does not cause oral dyskinesia (OD), but interacts with some substrate of brain aging, resulting in the premature emergence of OD, that can occur spontaneously with aging. In order to investigate a possible role of nigrostriatal dopaminergic supersensitivity and of oxidative stress in aging- and reserpine-induced OD, the stereotyped behavior induced by dopaminergic agonists, a functional index of dopaminergic striatal activity, as well as the striatal antioxidant enzymes glutathione peroxidase and catalase were assessed. We demonstrate that, opposite to normotensive Wistar rats (NWR), spontaneously hypertensive rats (SHR) do not develop aging- or reserpine-OD. There were no differences between NWR and SHR in stereotyped behavior or in striatal glutathione peroxidase activity. Adult and old SHR presented higher striatal catalase activity relative to NWR, and aging increased it only in SHR. The catalase inhibitor aminotriazole reverted the absence of aging- and reserpine-induced OD in SHR. Our results suggest an important role of striatal catalase in the development of reserpine- and aging-induced OD.

Role of hippocampal oxidative stress in memory deficits induced by sleep deprivation in mice.

Numerous animal and clinical studies have described memory deficits following sleep deprivation. There is also evidence that the absence of sleep increases brain oxidative stress. The present study investigates the role of hippocampal oxidative stress in memory deficits induced by sleep deprivation in mice. Mice were sleep deprived for 72 h by the multiple platform method-groups of 4-6 animals were placed in water tanks, containing 12 platforms (3 cm in diameter) surrounded by water up to 1 cm beneath the surface. Mice kept in their home cage or placed onto larger platforms were used as control groups. The results showed that hippocampal oxidized/reduced glutathione ratio as well as lipid peroxidation of sleep-deprived mice was significantly increased compared to control groups. The same procedure of sleep deprivation led to a passive avoidance retention deficit. Both passive avoidance retention deficit and increased hippocampal lipid peroxidation were prevented by repeated treatment (15 consecutive days, i.p.) with the antioxidant agents melatonin (5 mg/kg), N-tert-butyl-alpha-phenylnitrone (200 mg/kg) or vitamin E (40 mg/kg). The results indicate an important role of hippocampal oxidative stress in passive avoidance memory deficits induced by sleep deprivation in mice.

One-trial tolerance to the effects of chlordiazepoxide in the elevated plus-maze is not due to acquisition of a phobic avoidance of open arms during initial exposure.

A single exposure to the elevated plus-maze (EPM) test of anxiety reduces or abolishes the anxiolytic-like efficacy of benzodiazepines. This phenomenon called one-trial tolerance has been suggested to represent the acquisition of a phobic-like response to the open arms during trial 1. The present study was designed to examine the effects of chlordiazepoxide (5 mg/kg, ip) on the behaviour of rats in a conventional EPM apparatus after previous exposure to a four-open-arm EPM, a four-enclosed arm EPM or a conventional EPM, as well as in naive rats. Chlordiazepoxide had clear-cut anxiolytic-like effects (increased percentage of time spent on the open arms) in a traditional EPM in naive rats and in animals previously exposed to a four-open-arm EPM. However, it was ineffective in rats previously exposed to a traditional or a four-closed-arm EPM. Thus, the phenomenon of one-trial tolerance does not depend upon initial open-arm experience.

Effects of melatonin on orofacial movements in rats.

RATIONALE: While reserpine-induced oral movements (OM), an animal model of tardive dyskinesia, are more persistent in old than in adult rats, old animals present spontaneous OM, which are phenomenologically similar to those presented by reserpine-treated adult rats. We postulate that these OM may be the result of oxidative stress induced by both age and reserpine treatment. OBJECTIVES: We intended to determine the preventative effects of exogenous melatonin (one of the most important endogenous antioxidants) as well as suppression of endogenous melatonin via continuous exposure to light on reserpine- or age-induced OM in rats. METHODS: Adult (4 months of age) male Wistar rats were repeatedly treated with saline or melatonin (5 mg/kg, IP) and saline or reserpine and kept under a 12-h light/dark cycle for quantification of reserpine-induced OM as well as oxidative stress (via quantification of lipid peroxidation). To verify the effects of endogenous melatonin suppression on reserpine-induced OM, adult rats were repeatedly treated with saline or reserpine and continuously exposed to light. To verify the effects of exogenous melatonin on age-induced OM older (20 months of age) rats were long-term treated with saline or melatonin and kept under a 12-h light/dark cycle. RESULTS: Melatonin attenuated both reserpine- and age-induced OM. Reserpine enhanced striatal lipid peroxidation, that was prevented by melatonin co-administration. Continuous exposure to light increased spontaneous as well as reserpine-induced OM, indicating that endogenous melatonin may be involved in this movement disorder. CONCLUSIONS: We suggested that melatonin attenuates both reserpine- and age-induced OM in rats.

Involvement of nitric oxide in the pathogenesis of cyclophosphamide-induced hemorrhagic cystitis.

The involvement of nitric oxide (NO) and the potential modulation of NO synthase (NOS) activity by platelet-activating factor were investigated in a rat model of cyclophosphamide-induced hemorrhagic cystitis. Male Wistar rats received a single intraperitoneal injection of cyclophosphamide, and cystitis was evaluated 6, 12, 24, 48, and 72 hours later by determining the changes in bladder wet weight and plasma protein extravasation and the macro- and microscopic morphological alterations. In addition, NOS activity and NADPH-diaphorase histochemistry were studied in bladder tissues. Normal bladders showed extensive NADPH-diaphorase staining and a high level of constitutive NOS whereas the activity of inducible NOS was almost undetectable. Cyclophosphamide dose- and time-dependently increased the bladder wet weight and bladder plasma protein extravasation. These events were accompanied at a microscopic level by urothelial necrosis, sloughing, ulceration, hemorrhage, and leukocyte infiltration. Cyclophosphamide also increased the levels of inducible NOS but reduced those of constitutive NOS. The NOS inhibitors L-NG-nitroarginine methyl ester and L-NG-nitroarginine significantly reduced the cyclophosphamide-induced plasma protein extravasation and urothelial damage. This reduction was completely reversed by L-arginine but not by D-arginine. The administration of the platelet-activating factor antagonist BN 52021 decreased the cyclophosphamide-induced plasma protein extravasation as well as the rise in inducible NOS activity but had no effect on the fall in constitutive NOS activity. These results suggest that endogenous NO participates in the urothelial damage and in the inflammatory events leading to cyclophosphamide-induced hemorrhagic cystitis. Platelet-activating factor also seems to be involved in the pathogenesis of this condition, possibly by inducing NOS.

Acute diuretic effects in conscious rats produced by some medicinal plants used in the state of São Paulo, Brasil.

Extracts of 32 medicinal plants used popularly for their presumed diuretic and/or antihypertensive properties were tested for diuretic effects in conscious unrestrained rats. Extracts were made using aqueous ethanol (50:50, v/v) at 4-10 degrees C. When given orally at a dose of 40 ml/kg, a majority of the ethanol-free extracts produced a more pronounced diuresis than would be expected from the potassium concentration of the extracts. The most significant diuretic effect was observed with Hedychium coronarium sheath and leaf-blade extracts.

Acute antihypertensive effect in conscious rats produced by some medicinal plants used in the state of São Paulo.

Thirty two medicinal plants used popularly for their proposed diuretic and/or antihypertensive properties have been tested for antihypertensive effects in conscious unrestrained rats. All extractions were made in aqueous ethanol (50:50 by vol.) at low temperature. Before administration of the extracts the alcohol was evaporated. The extracts (40 ml/kg) were always administered per os. Antihypertensive effects in SHR rats were observed after the administration of Allium sativum Linn. (bulb), Olea europaea Linn. (leaf) and Hedychium coronarium Koen. (leaf-blade).