Tamoxifen antagonizes the effects of ovarian hormones to induce anxiety and depression-like behavior in rats / Tamoxifeno antagoniza os efeitos dos hormônios ovarianos que induzem comportamento similar a ansiedade e depressão em ratos

The effects of tamoxifen (TAM) on anxiety and depression-like behavior in ovariectomized (OVX) and naïve female rats were investigated. The animals were divided into Sham-TAM, OVX-TAM, Sham and OVX groups. Tamoxifen (1 mg/kg) was administered for 4 weeks. In the forced swimming test, the immobility times in the OVX and Sham-TAM groups were higher than in the Sham group. In the open field, the numbers of central crossings in the OVX and Sham-TAM groups were lower than the number in the Sham group, and the number of peripheral crossings in the OVX group was lower than the number in the Sham group. In the elevated plus maze, the numbers of entries to the open arm among the animals in the Sham-TAM and OVX groups were lower than the number in the Sham group, while the number of entries to the open arm in the OVX-TAM group was higher than the number in the OVX group. It was shown that deletion of ovarian hormones induced anxiety and depression-like behavior. Administration of tamoxifen in naïve rats led to anxiety and depression-like behavior that was comparable with the effects of ovarian hormone deletion. It can be suggested that tamoxifen antagonizes the effects of ovarian hormones. It also seems that tamoxifen has anxiolytic effects on ovariectomized rats.

Foram investigados os efeitos do tamoxifeno (TAM) no comportamento semelhante a ansiedade de depressão de ratas ooforectomizadas (OVX) e controles. Os animais foram divididos em Sham-TAM, OVX-TAM, Sham e OVX groups. Tamoxifeno (1 mg/kg) foi administrado por quatro semanas. No teste de natação forçada, os tempos de imobilidade nos grupos OVX e Sham-TAM foram maiores que aqueles do grupo Sham. No campo aberto, os números de cruzamento no centro nos grupos OVX e Sham-TAM foram menores que aquele do grupo Sham, e o número dos cruzamentos na periferia no grupo OVX foi menor que o número no grupo Sham. No labirinto elevado, os números de entradas com braços abertos entre os animais nos grupos Sham-TAM e OVX foram menores do que aqueles do grupo Sham, enquanto o número de entradas com os braços abertos no grupo OVX-TAM foi maior que aquele no grupo OVX. Foi observado que a deleção dos hormônios ovarianos induziu comportamento similar a ansiedade e depressão. A administração de tamoxifeno em ratos controle induziu a um comportamento que era comparável aos efeitos da deleção do hormônio ovariano. Pode ser sugerido que o tamoxifeno antagoniza os efeitos dos hormônios ovarianos. Parece também que o tamoxifeno tem efeito ansiolítico nas ratas ooforectomizadas.

Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats

Cocaine sensitization is a marker for some facets of addiction, is greater in female rats, and may be influenced by their sex hormones. We compared the modulatory effects of endogenous or exogenous estradiol and progesterone on cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized female rats received progesterone (0.5 mg/mL), estradiol (0.05 mg/mL), progesterone plus estradiol, or the oil vehicle. Sham-operated control females received oil. Control and acute subgroups received injections of saline, while the repeated group received cocaine (15 mg/kg, ip) for 8 days. After 10 days, the acute and repeated groups received a challenge dose of cocaine, after which locomotion and stereotypy were monitored. The estrous cycle phase was evaluated and blood was collected to verify hormone levels. Repeated cocaine treatment induced overall behavioral sensitization in female rats, with increased locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no locomotor sensitization; however, the sensitization of stereotypies was maintained. Only females with endogenous estradiol and progesterone demonstrated increased locomotor activity after cocaine challenge. Estradiol replacement enhanced stereotyped behaviors after repeated cocaine administration. Cocaine sensitization of stereotyped behaviors in female rats was reduced after progesterone replacement, either alone or concomitant with estradiol. The behavioral responses (locomotion and stereotypy) to cocaine were affected differently, depending on whether the female hormones were of an endogenous or exogenous origin. Therefore, hormonal cycling appears to be an important factor in the sensitization of females. Although estradiol increases the risk of cocaine sensitization, progesterone warrants further study as a pharmacological treatment in the prevention of psychostimulant abuse.

[ effect of intrathecal administration of cocaine and serotonergic antagonist [cyproheptadine] on nociception in rat]

Cocaine by effect on central nervous system inhibits reuptake of monoamines [serotonin, norepinephrine and dopamine] to presynaptic terminal and increases their concentration. Monoamines such as serotonin cause analgesia at the spinal level. This study investigates the effects of systemic and spinal administration of cocaine on pain sensation and the relation between these effects and serotonin. Male Wistar rats [200-250g] were set in groups: saline [i.p], saline/DMSO [i.p], cocaine 25mg/kg [i.p], saline [i.t], saline/DMSO [i.t], cocaine 100micro g/10 micro l [i.t], cyproheptadine 33 micro g/10 micro l [i.t.] and cyproheptadine 33 micro g/10 micro l/cocaine 100 micro g/10 micro l [i.t]. Tail flick latency was measured before and after administration. Intraplantar formalin was used for induction of chemical pain. The data was analyzed by T-Test and ANOVA. Pain in both phases of formalin test was reduced in both cocaine 25mg/kg [i.p] [P<0.01] and cocaine 100 micro g/10 micro l [i.t.] [P<0.01]. However, in cyproheptadine 33 micro g/10 micro l [i.t], was increased in the first phase [P<0.01]. In cyproheptadine 33 micro g/10 micro l/cocaine 100 micro g/10 micro l [i.t.], the part of pain reduction induced by cocaine was reversed, in both phases [P<0.01]. In tail flick test the results of cyproheptadine 33 micro g/10 micro l [i.t.] showed reduced tail flick latency [P<0.001]. Inhibition of serotonin reuptake at the spinal level plays role in analgesic effects of cocaine probably, because release of serotonin from the spinal serotonergic terminals causes inhibition of pain neurons and reduction of pain. In addition, inhibition of spinal serotonin receptors by cyproheptadine reduced part of analgesic effects of cocaine probably

Cambios en la hemodinamia cerebral en consumidores crónicos de paco y cocaína: estudio de casos y controles / [Changes in cerebral hemodynamics in chronic users of \"PACO\" and cocaine: case-control study].

OBJECTIVE: To assess if there are changes in brain hemodynamics evaluated by means of transcranial doppler’s flow velocity, pulsatile index and cerebral perfusion pressure, between cocaine chronic abusers and healthy volunteers. METHOD: Prospective, case and control, observational study. Sex, age, user history, vital signs and transcranial doppler findings.Statistical analysis was performed by means of normality test, Wilcoxon’s test for non parametric samples and T Student test. RESULTS: Fifty-three abusers and 35 healthy volunteers were studied. Statistical differences were found for a diminish in age(p=0.008) and cerebral perfusion pressure in all cerebral arteries (p

Manejo anestésico de paciente sob uso de cocaína e seus derivados mais utilizados / Anesthetic management of a patient under use of cocaine and its most used derivatives

Muitas das manifestações do uso de cocaína e seus derivados colocam o anestesista diante da difícil situação, como executar um manejo anestésico eficiente e seguro visto o grande número de alterações fisiopatológicas promovidas por essas drogas.

Many of the manifestations of cocaine and its derivatives pose the anesthetist before the predicament of how to run an efficient and safe anesthetic management since the large number pathophysiological changes promoted by these drugs.

Effects of cocaine on activities of ATPase, LDH and SDH in mouse splenocytes / 法医学杂志

OBJECTIVE@#To examine the effects of cocaine on the activities of ATPase, LDH and SDH in cultured mouse splenocytes in vitro.@*METHODS@#The ATPase, LDH and SDH activities in mouse splenocytes were detected at day 7 after continuous culturing the mouse cells exposed to cocaine hydrochloride in final concentration of 10, 20 and 100 microg/mL in vitro.@*RESULTS@#The activities of ATPase, LDH and SDH in mouse splenocytes exposed to cocaine hydrochloride in final concentration of 10, 20 and 100 microg/mL were significantly decreased after continuous culturing for 7 days.@*CONCLUSION@#The present study demonstrated that cocaine could inhibit the activities of ATPase, LDH and SDH in cultured splenocytes in vitro.

Daño endotelial y activación del sistema hemostático asociado al uso crónico de cocaína: estudios ex vivo e in vitro / Endothelial damage and activation of the haemostatic system associated to chronic use of cocaine: an ex vivo and in vitro study

Antecedentes: Usuarios crónicos de cocaína tienen riesgo aumentado de presentar infarto de miocardio, angina,muerte súbita y accidentes cerebrovasculares. Aunque la patogenia del daño vascular es mayormente desconocida, se ha encontrado arterioesclerosis prematura y formación de trombos intravasculares. Objetivo: Demostrar evidencia de daño endotelial y activación del sistema hemostático en usuarios crónicos de cocaína. Métodos: Un grupo de 23 pacientes con criterios de dependencia a cocaína DSM-IV; 19 hombres (edad promedio 32 a), con exposición a la droga dentro de 72 h del estudio. Disfunción endotelial se evaluó por enumeración de las células endoteliales circulantes (CEC) y nivel de sICAM . Para activación del sistema hemostático se incluyó: complejos trombina-antitrombina (TAT) y generación de trombina; NAP-2 y RANTES para activación plaquetaria. In vitro, CE en cultivo (HUVEC), se expusieron a plasma de consumidores o controles. Se midió factor von Willebrand (FVW) en el medio y expresión de FvW y factor tisular (FT) sobre las CE. Adhesión plaquetaria estática se evaluó por microscopía. Resultados: En usuarios de cocaína, con respecto a controles, las CEC estaban significativamente elevadas...

Background: chronic cocaine users have an increased risk of developing myocardial infarction, angina, suddendeath and stroke. Although the pathogenesis of this effect is not completely known, premature atheromatosis and intravascular thrombosis appear to be involved.Aim: to provide evidence for the presence of endothelial damage and activation of the haemostatic system in chronic cocaine users. Methods: 23 subjects (19males, overall mean age 32) with DSM-IV criteria for cocaine dependency and exposure to the drug within 72 hours were studied. Endothelial dysfunction was determined by circulating endothelial cell counts (CEC) and sICAM levels. Thrombin-antithrombin complexes (TAT) and thrombin generation were used to characterize haemostatic status. In vitro, platelet activation was studied by NAP-2 and RANTES. EC in culture (HUVEC) were exposed to plasma from cocaine users and controls. Von Willebrand factor was measured in the culture media as well as its expression along with that of tissue factor in EC. Platelet adhesion was evaluated by microscopy. Results: Compared to controls, EC were significantly increased in cocaine users...

Influence of progesterone on GAD65 and GAD67 mRNA expression in the dorsolateral striatum and prefrontal cortex of female rats repeatedly treated with cocaine

Female rats are intensely affected by cocaine, with estrogen probably playing an important role in this effect. Progesterone modulates the GABA system and attenuates the effects of cocaine; however, there is no information about its relevance in changing GABA synthesis pathways after cocaine administration to female rats. Our objective was to investigate the influence of progesterone on the effects of repeated cocaine administration on the isoenzymes of glutamic acid decarboxylase (GAD65 and GAD67) mRNA in brain areas involved in the addiction circuitry. Ovariectomized, intact and progesterone replacement-treated female rats received saline or cocaine (30 mg/kg, ip) acutely or repeatedly. GAD isoenzyme mRNA levels were determined in the dorsolateral striatum (dSTR) and prefrontal cortex (PFC) by RT-PCR, showing that repeated, but not acute, cocaine decreased GADs/β-actin mRNA ratio in the dSTR irrespective of the hormonal condition (GAD65: P < 0.001; and GAD67: P = 0.004). In the PFC, repeated cocaine decreased GAD65 and increased GAD67 mRNA ratio (P < 0.05). Progesterone replacement decreased both GAD isoenzymes mRNA ratio after acute cocaine in the PFC (P < 0.001) and repeated cocaine treatment reversed this decrease (P < 0.001). These results suggest that cocaine does not immediately affect GAD mRNA expression, while repeated cocaine decreases both GAD65 and GAD67 mRNA in the dSTR of female rats, independently of their hormonal conditions. In the PFC, repeated cocaine increases the expression of GAD isoenzymes, which were decreased due to progesterone replacement.

Complicaciones medicas asociadas al consumo de cocaína

La utilización de las hojas de coca por parte de las culturas incaicas enmarcadas en sus costumbres cotidianas como estimulantes, ahorrador de energías y protector del hambre junto con algunos elementos chamánicos reservados a la casta religiosa o más alta, fueaprovechada por los descubridores españoles de las Américas para explotar laboralmente a las tríbus indígenas. Pero la verdadera exclosión se produce con el descubimiento en el siglo XIX de su alcaloide: la cocaína. Ensalzada desde el punto de vista médico y social hasta principios del siglo XX, prohibida posteriormente por la aparición de consecuencias sobre todo de orden psicológico y la constatación de su capacidad adictiva, esto no ha sido impedimento para que se haya convertido en nuestros días en una de las drogas más consumidas, generando enormes beneficios en el mercado negro y permitiendo la aparición de nuevas formas más peligrosas y adictivas que la propia cocaína.

Effects of cocaine, methamphetamine and modafinil challenge on sleep rebound after paradoxical sleep deprivation in rats

Sleep loss is both common and critically relevant to our society and might lead to the abuse of psychostimulants such as amphetamines, cocaine and modafinil. Since psychoactive substance abuse often occurs within a scenario of sleep deficit, the purpose of this investigation was to compare the sleep patterns of rats challenged with cocaine (7 mg/kg, ip), methamphetamine (7 mg/kg, ip), or modafinil (100 mg/kg, ip) subsequent to paradoxical sleep deprivation (PSD) for 96 h. Our results show that, immediately after 96 h of PSD, rats (10 per group) that were injected with a psychostimulant presented lower percentages of paradoxical sleep compared to those injected with saline (P < 0.01). Regarding slow wave sleep (SWS), rats injected with psychostimulants after PSD presented a late rebound (on the second night subsequent to the injection) in the percentage of this phase of sleep when compared to PSD rats injected with saline (P < 0.05). In addition, the current study has produced evidence of the characteristic effect of each drug on sleep architecture. Home cage control rats injected with modafinil and methamphetamine showed a reduction in SWS compared with the saline group. Methamphetamine affected sleep patterns most, since it significantly reduced paradoxical sleep, SWS and sleep efficiency before and after PSD compared to control (P < 0.05). Cocaine was the psychostimulant causing the least changes in sleep pattern in relation to those observed after saline injection. Therefore, our results suggest that abuse of these psychostimulants in a PSD paradigm aggravates their impact on sleep patterns.

Anestesia no paciente usuário de cocaína / Anesthesia in cocaine users

JUSTIFICATIVA E OBJETIVOS: A cocaína é a droga ilícita mais freqüentemente associada a óbitos, e suas implicações perioperatórias nos pacientes agudamente intoxicados ou com história de uso crônico precisam ser bem conhecidas pelos anestesiologistas. O conhecimento da neurofisiologia, da farmacologia e das conseqüências fisiopatológicas decorrentes do uso da cocaína poderá facilitar o cuidado desses pacientes. O objetivo deste trabalho foi revisar as informações sobre a cocaína e suas interações com a anestesia. CONTEUDO: O artigo discute a farmacologia da cocaína, as conseqüências fisiopatológicas decorrentes do seu uso e as interações com a anestesia. CONCLUSÕES: A compreensão e o reconhecimento precoce das complicações associadas ao uso de cocaína são essenciais para o manuseio adequado de pacientes usuários desta droga. O anestesiologista deve estar preparado, pois tanto as anestesias regionais quanto a geral apresentam riscos significativos nesses pacientes.

BACKGROUND AND OBJECTIVES: Cocaine is the illicit drug most frequently associated with death, and the anesthesiologist should be aware of the perioperative complications of this drug in patients with acute intoxication or with a history of chronic use. The knowledge of the neurophysiology, pharmacology, and physiopathological consequences of cocaine abuse may facilitate the care of these patients. The objective of this work was to review the information on cocaine and its interactions with anesthesia. CONTENTS: This paper discusses the pharmacology, physiopathological consequences of cocaine use, and its interactions with anesthesia. CONCLUSIONS: The knowledge and early recognition of the complications associated with the use of cocaine are essential for the adequate management of cocaine users. The anesthesiologist should be prepared because both regional and general anesthesia carry significant risks in those patients.

JUSTIFICATIVA Y OBJETIVOS: La cocaína es la droga ilícita más frecuentemente asociada a decesos, y sus implicaciones perioperatorias en los pacientes agudamente intoxicados o con historial de uso crónico necesitan ser muy bien conocidas por los anestesiólogos. El conocimiento de la neurofisiología, de la farmacología y de las consecuencias fisiopatológicas provenientes del uso de la cocaína podrá facilitar el cuidado de esos pacientes. El objetivo de este trabajo fue revisar las informaciones sobre la cocaína y sus interacciones con la anestesia. CONTENIDO: El artículo discute la farmacología de la cocaína, las consecuencias fisiopatológicas provenientes de su uso y las interacciones con la anestesia. CONCLUSIONES: La comprensión y el reconocimiento precoz de las complicaciones asociadas al uso de la cocaína son esenciales para el manejo adecuado de pacientes usuarios de esa droga. El anestesiólogo debe estar preparado, pues tanto las anestesias regionales como la general presentan riesgos significativos en esos pacientes.

Complicaciones cardiovasculares por uso de cocaína / Cardiovascular complications due to cocaine

La cocaína es la segunda droga ilegal de mayor consumo en Chile, ya sea como clorhidrato o como pasta base de cocaína. Hemos reportado que el 6 por ciento de los pacientes que ingresaron con Infarto Agudo del Miocardio con supradesnivel del ST (IAMSDST) declararon haber consumido cocaína en la semana previa al evento y la cifra real podría ser mayor. Los efectos cardiovasculares de la cocaína son causados por la inhibición de la recaptura de la noradrenalina en las terminaciones simpáticas, causando vasoespasmo, trombosis coronaria, cardiotoxicidad y aumento del consumo de O2 por taquicardia e hipertensión arterial. Los pacientes con IAM secundario al uso de cocaína son con frecuencia jóvenes que han consumido cocaína en las últimas 24 horas. El diagnóstico de isquemia o infarto en estos pacientes es difícil; el electrocardiograma puede no ser específico hasta en el 60 por ciento delos casos. Se deben utilizar troponinas como marcadores de necrosis, pues las CK-MB dan falsos positivos. El tratamiento incluye hospitalización, benzodiazepinas, morfina IV, nitratos, calcioantagonistas y oxígeno. Debe evitarse el uso de betabloqueadores, porque aumentan la vasoconstricción al liberar el tono a adrenérgico. Ante un IAMSDST, los trombolíticos deben ser usados con precaución, pues se ha reportado una mayor incidencia de hemorragia cerebral. La mejor terapia de reperfusión coronaria en estos casos es la angioplastía primaria.

Cocaine is the second most commonly used drug of abuse in Chile. We reported that 6 percent of patients with STEMI have used cocaine during the week previous to the event, number that could be higher. Cocaine inhibits catecholamine reuptake, resulting in a hyperadrenergic state, which may induce vasospasm, coronary thrombosis, cardiotoxicity, increased myocardial O2 consumption and severe hypertension. Patients with cocaine induced chest pain are frequently young men that had consumed the drug during the last 24 hours. The ECG is specific only in about 60 percent of cases. Troponins should be used to confirm AMI; CK-MB may give false positive results. Treatment of cocaine induced chest pain includes hospitalization, benzodiazepines, nitroglycerin, calcium channel blockers, IV morphine and O2. beta-blockers should not be used because they could increase vasospasm, due to unopposed alpha adrenergic tone. When STEMI is diagnosed, primary angioplasty is the preferred reperfusion method. Thrombolysis is not a first option due to increased rates of intracerebral hemorrhage in cocaine users.

Behavioral changes induced by cocaine in mice are modified by a hyperlipidic diet or recombinant leptin

The objective of the present study was to determine if the acute behavioral effects of cocaine acutely administered intraperitoneally (ip) at doses of 5, 10 and 20 mg/kg on white male CF1 mice, 90 days of age, would be influenced by leptin acutely administered ip (at doses of 5, 10 and 20 æg/kg) or by endogenous leptin production enhanced by a high-fat diet. The acute behavioral effects of cocaine were evaluated in open-field, elevated plus-maze and forced swimming tests. Results were compared between a group of 80 mice consuming a balanced diet and a high-fat diet, and a group of 80 mice fed a commercially available rodent chow formula (Ralston Purina) but receiving recombinant leptin (rLeptin) or saline ip. Both the high-fat-fed and rLeptin-treated mice showed decreased locomotion in the open-field test, spent more time in the open arms of the elevated plus-maze and showed less immobility time in the forced swimming test (F(1,68) = 7.834, P = 0.007). There was an interaction between diets and cocaine/saline treatments in locomotion (F(3,34) = 3.751, P = 0.020) and exploration (F(3,34) = 3.581, P = 0.024). These results suggest that anxiolytic effects and increased general activity were induced by leptin in cocaine-treated mice and that low leptin levels are associated with behavioral depression. Chronic changes in diet composition producing high leptin levels or rLeptin treatment may result in an altered response to cocaine in ethologic tests that measure degrees of anxiety and depression, which could be attributed to an antagonistic effect of leptin.

Cocaína: investigación bibliográfica / Cocaine: bibliographical investigation

Se trata de una revisión bibliográfica sobre las principales características farmacológicas, clínicas y de tratamiento de la intoxicación con cocaína, así mismo incluye otros aspectos tratados menos frecuentes en la literatura médica como las características botánicas de la planta de Coca y una breve historia del consumo y prohibición de la coca y la cocaína desde los Incas al siglo XX. Se han incluido datos estadísticos actualizados del consumo de cocaína y crack en nuestro país producto de las investigaciones de Instituto sobre Alcoholismo y Farmacodependencia (IAFA) al respecto.

Drogas en el Perú / Drugs in Peru

Bajo el título de drogas en el Perú se presenta un apretado resumen de la farmacología de las drogas ilícitas de uso más extendido en el país. No se ha considerado pertinente presentar en esta oportunidad la gran familia de las drogas de las que se abusa frecuentemente pero que por razones epidemiológicas y de manejo de los aspectos preventivos se clasifican como drogas sociales, productos industriales o drogas folclóricas. El libro ha sido diseñado como un auxiliar práctico para público general, maestros y alumnos que requieran obtener información farmacológica acerca de las drogas en un lenguaje accesible al público general. Ramiro Castro de la Mata, médico farmacólogo especialista en drogas y miembro fundador de CEDRO, presenta en esta obra, una apretada síntesis de los principales aspectos de la farmacología de las principales drogas ilícitas cuyo consumo viene aquejando a la población peruana o de aquellas como el opio que amenazan a las futuras generaciones