O extrato bruto hidroalcoólico das folhas de Piper caldense C. DC. na redução do consumo de álcool em ratos / The hydroalcoholic extract of leaves of Piper caldense C. DC. decreases alcohol consumption in rats

A investigação de plantas medicinais como recurso terapêutico para combater o alcoolismo ainda é muito insipiente com poucas espécies investigadas. No presente trabalho avaliamos o efeito do extrato hidroalcoólico das folhas da planta Piper caldense C. DC. com relação ao consumo de álcool e também a sua potencialidade ansiolítica. Foram utilizados ratos Wistar machos, os quais foram divididos em grupos controle (solução fisiológica) e tratado (extrato da planta nas doses de 25, 50 e 150 mg/kg, e diazepam 2 mg/kg). Os animais foram tratados através da via intraperitoneal 1 h antes dos experimentos. Os modelos animais utilizados foram: Labirinto em Cruz Elevado (LCE) e auto-administração de álcool (AA). No LCE o extrato não apresentou efeito ansiolítico do tipo benzodiazepínico. Por outro lado, no comportamento relacionado a auto-administração de solução de álcool, o extrato apresentou efeito significativo reduzindo o consumo de álcool em relação ao grupo controle. Apesar do extrato não ter apresentado efeito ansiolítico, o mesmo parece apresentar potencialidades para combater o abuso e a dependência de álcool.

The investigation of medicinal plants as therapeutic resources in the combat of alcoholism is still very incipient with few species being investigated. The purpose of the present study was to examine the effects of the hydroalcoholic extract of leaves of Piper caldense C. DC. in relation to alcohol consumption and also its anxiolytic potentiality. Male Wistar rats, which had been separated into control group (saline) and treated group (Plant extract doses of 25, 50 and 150 mg/kg and 2 mg/kg of diazepam), were used. Animals were injected intraperitoneally 1 h before the tests. The following models were used: Elevated plus maze (EPM) and alcohol self-administration (ASA). In the EPM, the extract did not show benzodiazepine anxiolytic effect. On the other hand, in the behavior related to alcohol self-administration, the extract showed a significant effect, reducing alcohol consumption compared to the control group. Although the extract has not shown any anxiolytic effect, the results suggest that the plant has potential to combat alcohol abuse and addiction.

Comparison of voluntary ethanol intake by two pairs of rat lines used as genetic models of anxiety

The relationship between anxiety-related behaviors and voluntary ethanol intake was examined in two pairs of rat lines by the oral ethanol self-administration procedure. Floripa high (H) and low (L) rats selectively bred for contrasting anxiety responses in the open-field test, and two inbred strains, spontaneously hypertensive rats (SHR) and Lewis rats which are known to differ significantly when submitted to several behavioral tests of anxiety/emotionality, were used (9-10 animals/line/sex). No differences in the choice of ethanol solutions (2 percent, days 1-4, and 4 percent, days 5-8, respectively) in a 2-bottle paradigm were detected between Floripa H and L rats (1.94 ± 0.37 vs 1.61 ± 0.37 g/kg for ethanol intake on day 8 by the Floripa H and L rat lines, respectively). Contrary to expectations, the less anxious SHR rats consumed significantly more ethanol than Lewis rats (respective intake of 2.30 ± 0.45 and 0.72 ± 0.33 g/kg on day 8) which are known to be both addiction-prone and highly anxious. Regardless of strain, female rats consumed more ethanol than males (approximately 46 percent). The results showed no relationship between high anxiety and voluntary intake of ethanol for Floripa H and L rats. A negative association between these two variables, however, was found for SHR and Lewis rat strains. Data from the literature regarding the association between anxiety and alcohol intake in animal models are not conclusive, but the present results indicate that factors other than increased inborn anxiety probably lead to the individual differences in ethanol drinking behavior.

Comparison of voluntary ethanol intake by two pairs of rat lines used as genetic models of anxiety.

The relationship between anxiety-related behaviors and voluntary ethanol intake was examined in two pairs of rat lines by the oral ethanol self-administration procedure. Floripa high (H) and low (L) rats selectively bred for contrasting anxiety responses in the open-field test, and two inbred strains, spontaneously hypertensive rats (SHR) and Lewis rats which are known to differ significantly when submitted to several behavioral tests of anxiety/emotionality, were used (9-10 animals/line/sex). No differences in the choice of ethanol solutions (2%, days 1-4, and 4%, days 5-8, respectively) in a 2-bottle paradigm were detected between Floripa H and L rats (1.94 +/- 0.37 vs 1.61 +/- 0.37 g/kg for ethanol intake on day 8 by the Floripa H and L rat lines, respectively). Contrary to expectations, the less anxious SHR rats consumed significantly more ethanol than Lewis rats (respective intake of 2.30 +/- 0.45 and 0.72 +/- 0.33 g/kg on day 8) which are known to be both addiction-prone and highly anxious. Regardless of strain, female rats consumed more ethanol than males (approximately 46%). The results showed no relationship between high anxiety and voluntary intake of ethanol for Floripa H and L rats. A negative association between these two variables, however, was found for SHR and Lewis rat strains. Data from the literature regarding the association between anxiety and alcohol intake in animal models are not conclusive, but the present results indicate that factors other than increased inborn anxiety probably lead to the individual differences in ethanol drinking behavior.

Rapid tolerance to Delta(9)-tetrahydrocannabinol and cross-tolerance between ethanol and Delta(9)-tetrahydrocannabinol in mice.

Motor incoordination in the rota-rod test was used to assess the development of rapid tolerance to Delta(9)-tetrahydrocannabinol and rapid cross-tolerance between ethanol and Delta(9)-tetrahydrocannabinol in mice. Further, the influence of the cannabinoid receptor antagonist SR 141716A (N-(piperidin-1-yl)-5-(4-chlorophenyl)-4-methyl-1H-pyrazole-3-carboxyamide) on the motor impairment induced by both drugs was examined. Mice were injected on day 1 with equipotent doses of Delta(9)-tetrahydrocannabinol (28 mg/kg, i.p.) and ethanol (2.25 g/kg, i.p.) and tested at 30, 60 and 90 min after the injections. On day 2, control groups received ethanol or Delta(9)-tetrahydrocannabinol, some groups received the same treatment as the day before, while the remaining groups switched the treatment. All groups were tested to evaluate tolerance. The development of rapid tolerance to Delta(9)-tetrahydrocannabinol was observed and pretreatment with ethanol resulted in rapid cross-tolerance to Delta(9)-tetrahydrocannabinol. SR 141716A (2 mg/kg, i.p.) failed to block the development of rapid tolerance to both drugs, ethanol and Delta(9)-tetrahydrocannabinol. These results suggest that Delta(9)-tetrahydrocannabinol, similarly to ethanol, can induce rapid tolerance to motor incoordination in mice. They also support the use of the 2-day protocol as an effective procedure to reduce the length of drug exposure necessary to induce tolerance.