RESUMO
RATIONALE: The hallucinatory effect and potential abuse of salvinorin A, the major ingredient of Salvia divinorum, has not been documented in animals. OBJECTIVE: The effects of salvinorin A on the zebrafish (Danio rerio) model, through its swimming behavior and conditioned place preference (CPP) task, was studied. MATERIALS AND METHODS: Swimming activity was determined in a squared observational chamber after an i.m. treatment of salvinorin A (0.1-10 microg/kg). For the CPP test, zebrafish were given salvinorin A (0.2 and 1 microg/kg) or vehicle and evaluated in a two-compartment chamber. RESULTS: Salvinorin A (0.1 and 0.2 microg/kg) induced accelerated swimming behavior in comparison with vehicle, whereas a "trance-like" effect, at doses as 5 and 10 microg/kg, was obtained. Pretreatment with the kappa-opioid antagonist, nor-binaltorphimine (nor-BNI; 10 mg/kg) and the cannabinoid type 1 (CB(1)) antagonist, rimonabant (1 mg/kg), blocked salvinorin A-induced both stimulating and depressive effects obtained at a dose of 0.2 and 10 microg/kg, respectively. In the CPP test, salvinorin A (0.2 and 0.5 microg/kg) produced an increase in the time spent in the drug-associated compartment. A dose of 1 microg/kg produced no effect, whereas a dose of 80 microg/kg induced aversion. Pretreatment with nor-BNI or rimonabant fully reversed the reinforcing properties of salvinorin A (0.5 microg/kg). CONCLUSIONS: Taken together, these results indicate that salvinorin A, as is sometimes reported in humans, exhibits rewarding effects, independently from its motor activity, suggesting the usefulness of the zebrafish model to study addictive behavior. These effects appear mediated by activation of both kappa-opioid and cannabinoid CB(1) receptors.
Assuntos
Comportamento Aditivo/metabolismo , Comportamento Animal/efeitos dos fármacos , Diterpenos/farmacologia , Alucinógenos/farmacologia , Receptor CB1 de Canabinoide/efeitos dos fármacos , Receptores Opioides kappa/efeitos dos fármacos , Peixe-Zebra/metabolismo , Animais , Condicionamento Psicológico/efeitos dos fármacos , Diterpenos Clerodânicos , Relação Dose-Resposta a Droga , Modelos Animais , Atividade Motora/efeitos dos fármacos , Naltrexona/análogos & derivados , Naltrexona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Piperidinas/farmacologia , Pirazóis/farmacologia , Receptor CB1 de Canabinoide/metabolismo , Receptores Opioides kappa/metabolismo , Reforço Psicológico , Reprodutibilidade dos Testes , Recompensa , Rimonabanto , Natação , Fatores de TempoRESUMO
We examined the toxicity of cocatropine (cocaine/atropine mixture) and the therapeutic potential of diazepam on some behavioral and physiological parameters in rats. Atropine (20 and 60 mg/kg) or cocaine (40 mg/kg) alone did not induce any seizure or death, but the combination significantly increased both, after both acute and binge treatment. There was a significant increase of EEG mean total spectral power in cocatropine- in comparison with cocaine-treated animals. Hyperlocomotion was observed in non-seizuring rats treated with cocaine or cocatropine. Cocaine, atropine 60, and cocatropine (40 + 20 and 40 + 60) all induced hyperthermic effects in non-seizuring rats, while cocatropine (40 + 60)-seizuring animals had hypothermia. An initial hypertensive and tachycardiac effect within 15 min was followed by a secondary fall in the cocatropine (40 + 60) group. Cocatropine toxicity was partially or fully reversed by diazepam (5 mg/kg), given intraperitoneally after the first seizure. The present findings provide, for the first time, details of a synergistic toxic effect of the cocaine/atropine mixture and of the potential of diazepam for treating cocatropine-related hospital emergencies.
Assuntos
Anticonvulsivantes/farmacologia , Atropina/toxicidade , Cocaína/toxicidade , Diazepam/farmacologia , Animais , Atropina/administração & dosagem , Temperatura Corporal/efeitos dos fármacos , Cocaína/administração & dosagem , Inibidores da Captação de Dopamina/administração & dosagem , Inibidores da Captação de Dopamina/toxicidade , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Eletroencefalografia , Masculino , Atividade Motora/efeitos dos fármacos , Parassimpatolíticos/administração & dosagem , Parassimpatolíticos/toxicidade , Ratos , Ratos Wistar , Convulsões/induzido quimicamente , Convulsões/prevenção & controleRESUMO
BACKGROUND: The recreational drug, Salvinorin A, derived from the plant of Salvia divinorum, is a potent and selective kappa-opioid receptor agonist. The abuse of selective k-agonists is a novel phenomenon, the mechanism of which is not fully understood. METHODS: We investigated salvinorin A given SC on the conditioned place preference (.05-160 microg/kg) and intracerebroventricular (ICV) self-administration (.01-1 microg/infusion) paradigms, in Wistar rats. RESULTS: The present results demonstrate the rewarding effects of Salvinorin A in a range of doses between .1 and 40 microg/kg SC for conditioned place preference test and .1-.5 microg/infusion for ICV self-administration. Highest doses (160 microg/kg for conditioned place preference test and 1 microg/infusion for ICV self-administration) were aversive. The rewarding effect was antagonized by intraperitoneal (IP) pretreatment with the cannabinoid CB(1) receptor antagonist, rimonabant [N-piperidino-5-(4-chlorophenyl)1-(2,4-dichloro phenyl)-4 methyl pyrazole 3-carboxamide] (1 mg/kg), and the kappa-opioid receptor antagonist, nor-binaltorphimine (nor-BNI) (10 mg/kg). In the shell of nucleus accumbens, dopamine extracellular levels were increased after administration of salvinorin A (40 microg/kg SC), reaching a maximum value of about 150%. CONCLUSIONS: These data provide the demonstration of the rewarding effects of Salvinorin A through an interaction between kappa-opioid and (endo)cannabinoid system in rats.
Assuntos
Antioxidantes/farmacologia , Moduladores de Receptores de Canabinoides/fisiologia , Condicionamento Operante/efeitos dos fármacos , Diterpenos/farmacologia , Endocanabinoides , Receptores Opioides kappa/fisiologia , Recompensa , Análise de Variância , Animais , Comportamento Animal/efeitos dos fármacos , Moduladores de Receptores de Canabinoides/antagonistas & inibidores , Diterpenos Clerodânicos , Dopamina/metabolismo , Relação Dose-Resposta a Droga , Vias de Administração de Medicamentos , Interações Medicamentosas , Masculino , Microdiálise/métodos , Atividade Motora/efeitos dos fármacos , Naltrexona/análogos & derivados , Naltrexona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Piperidinas/farmacologia , Pirazóis/farmacologia , Ratos , Ratos Wistar , Rimonabanto , AutoadministraçãoRESUMO
INTRODUCTION: Historically chocolate has been reported to exert several effects on human sexuality, mainly acting as an effective aphrodisiac, increasing sexual desire, and improving sexual pleasure. AIM: The aim of our study was to assess whether there is an association between daily chocolate intake and sexual function in a convenience sample of Northern Italian women. METHODS: A convenience sample of 163 women (mean +/- SD age: 35.3 +/- 9.2 years; body mass index [BMI]: 22.5 +/- 3.5 kg/m2), recruited through advertising, completed an anonymous semistructured interview on recreational habits and questionnaires to assess sexual function (Female Sexual Function Index [FSFI]), sexual distress (Female Sexual Distress Scale), and depression (Beck Depression Inventory and Center for Epidemiological Survey Depression Scale). RESULTS: Complete data were available for 153/163 (93.8%) women. Participants who reported daily chocolate intake (Group 1: 120 women) were significantly younger than those (Group 2: 33 women) who did not report to eat chocolate (33.9 +/- 0.8 years vs. 40.4 +/- 1.6 years, respectively) (P = 0.0003), despite a similar BMI. Participants in Group 1 had significantly higher total (P = 0.002) and desire domain (P = 0.01) FSFI scores than participants in Group 2. No differences between the two groups were observed concerning sexual arousal and satisfaction, sexual distress and depression. Our data also confirm that aging has a high statistically significant impact on women's sexual function. CONCLUSIONS: It is alluring to hypothesize that chocolate can have either a psychological or a biological positive impact on women's sexuality. In our sample women reporting chocolate consumption have higher FSFI scores than women who do not eat chocolate. However, when data are adjusted for age FSFI scores are similar, regardless of chocolate consumption.