Involvement of the extracellular signal-regulated kinase cascade for cocaine-rewarding properties

A central feature of drugs of abuse is to induce gene expression in discrete brain structures that are critically involved in behavioral responses related to addictive processes. Although extracellular signal-regulated kinase (ERK) has been implicated in several neurobiological processes, including neuronal plasticity, its role in drug addiction remains poorly understood. This study was designed to analyze the activation of ERK by cocaine, its involvement in cocaine-induced early and long-term behavioral effects, as well as in gene expression. We show, by immunocytochemistry, that acute cocaine administration activates ERK throughout the striatum, rapidly but transiently. This activation was blocked when SCH 23390 [a specific dopamine (DA)-D1 antagonist] but not raclopride (a DA-D2 antagonist) was injected before cocaine. Glutamate receptors of NMDA subtypes also participated in ERK activation, as shown after injection of the NMDA receptor antagonist MK 801. The systemic injection of SL327, a selective inhibitor of the ERK kinase MEK, before cocaine, abolished the cocaine-induced ERK activation and decreased cocaine-induced hyperlocomotion, indicating a role of this pathway in events underlying early behavioral responses. Moreover, the rewarding effects of cocaine were abolished by SL327 in the place-conditioning paradigm. Because SL327 antagonized cocaine-induced c-fos expression and Elk-1 hyperphosphorylation, we suggest that the ERK intracellular signaling cascade is also involved in the prime burst of gene expression underlying long-term behavioral changes induced by cocaine. Altogether, these results reveal a new mechanism to explain behavioral responses of cocaine related to its addictive properties.

Smoked cocaine in socially-depressed areas

Background: The main objectives of this study are to describe the smoked cocaine user's profile in socially-depressed areas and their needs from a harm-reduction perspective, to investigate their use of smoking crack and compare the acute effects between injecting and smoking consumption. Methods: The study took place in SAPS, Barcelona, Spain. Two focus group sessions were undertaken with a total of 8 drug users. Secondly, the 8 participants answered a structured questionnaire and in the course of the sessions, as a snowball activity, were trained to survey 6 other crack smokers. Results: We obtained 56 questionnaires. The majority of participants were from non-European Community countries (62.69%), 70.2% of participants referred to sharing the smoking equipment. The most frequent symptoms reported during smoked cocaine were mydriasis (83.33%)), perspiration (72.92%) and compulsive object search (70.83%) During the group sessions, participants said that smoked cocaine is much more addictive than injected cocaine and causes more anxiety. Participants also reported the difficulty of changing from injected use to smoked use, due to the larger amount of cocaine needed to reach the same effects as when having injected. Conclusions We can conclude that the research, focused on achieving greater knowledge of the smoked cocaine user's profile, their usage of smoking crack, consumption patterns and acute effects, should be incorporated into substance misuse interventions.

Passes fins a futurs canvis legislatius a l’àmbit penal en material de conducció de vehicles. Estudi quantitatiu de cocaïna i heroïna en saliva de conductors

Estudi de la presència de cocaïna i opiacis en saliva, en subjectes sospitosos de conduir sota els efectes de les drogues. Aplicació d’un test d’immunoassaig (Cozart). Confirmació i quantificació dels resultats positius (CG-EM). Comparació amb alteracions clíniques en els subjectes. No hi ha diferències entre concentracions de droga i signes clínics avaluades

Drogues d’abús en detinguts al jutjat de guàrdia: repercusió a l’àmbit de l’execució penal i l’Administració de justícia

L’estudi de la saliva com a matriu d’anàlisis de drogues d’abús en conductors es fa des dels anys 80. Els investigadors trobaven dificultats però el major inconvenient va ser l’existència de tècniques analítiques no prou sensibles per a la detecció de les drogues. A finals de les anys 90 la saliva es va considerar un fluid molt adequat i es van anar publicant treballs que investigaven aquesta temàtica. No obstant això encara no n ’hi ha molts treballs, especialment al nostre país. A Catalunya no s’han fet estudis encara que s’ha contribuït en alguns projectes realitats fora de la nostra comunitat. Objectius: Obtenir dades del consum de drogues d’abús en una mostra de conductors de vehicles a motor. Obtenir dades dels tòxics més freqüents trobats en les mostres analitzades. Relacionar el consum de tòxics amb alteracions en la conducta o conduccions temeràries en la població que es sotmet a l’estudi. Metodologia: Estudi d’una mostra de subjectes que són aturats per la Guàrdia Urbana de Barcelona, Girona ,Tarragona i policia local de el Prat de Llobregat conduint vehicles a motor. Obtenció d’una mostra de saliva als subjectes que es consideren que poden trobar-se sota la influència de les drogues. Anàlisis de les mostres per immunoassaig mitjançant el kit Cozart DDS com a test de camp i confirmació dels resultats per cromatografia de gasos i espectrometria de masses. Resultats: Es descriuen en els resultats obtinguts, les freqüències de consum, les principals drogues d’abús trobades i es valoren els símptomes clínics que presentaven els subjectes. Conclusions: Les drogues d’abús estan presents en conductors de vehicles a motor. El kit utilitzat per la determinació de drogues a peu de carretera és una bona eina atès que es confirmen els resultats especialment per a la cocaïna i opiacis.

Creencias sesgadas respecto al grado de "dureza" de algunas drogas en estudiantes universitarios

El objetivo de esta investigación es evaluar las creencias de los estudiantes universitarios respecto a la dureza de diez drogas: anfetaminas, café, heroína, barbitúricos, marihuana, ansiolíticos, tabaco, alcohol, cocaína y té. Ciento cincuenta y cinco estudiantes de Psicología debían indicar si creían que estas sustancias eran o no drogas duras. Los resultados indican que aunque existe consenso a la hora de clasificar como drogas duras a la heroína y la cocaína y como drogas blandas al tabaco, el café y el té, no existe acuerdo respecto a la clasificación de las otras sustancias. Asimismo se observa que aunque la OMS clasifica el alcohol como una droga altamente peligrosa, menos de la mitad de sujetos lo consideran una droga dura. En general los sujetos tienden a considerar las drogas legales como menos duras independientemente de si los efectos nocivos para la salud. Estos resultados adquieren relevancia cuando lo que se pone en juego es la fiabilidad y validez de los datos obtenidos en diferentes investigaciones que utilizan habitualmente esos conceptos

El consum de drogues i cocaïna dels joves de l’IES Miquel Martí i Pol de Roda de Ter

En l’actualitat, l’ús i el consum de substàncies il·legals pels joves de l’IES Miquel Martí i Pol de Roda de Ter és un fenomen associat a l’oci, per tant es tracta d’un consum recreatiu per fer referència al consum que fan els joves que el que busquen és diversió i plaer, moltes vegades, sense percebre’n el risc. Pel que fa a les drogues legals, alcohol i tabac són les substàncies psicoactives de major consum. La cocaïna és pels joves la segona substància consumida, rere el cànnabis, que és la més estesa entre la població adolescent i joves de l’IES. Es pot dir que existeixen una sèrie de situacions de caràcter personal i social que poden predisposar certes persones a consumir drogues. Aquestes circumstàncies són els anomenats factors de risc, com són l’autoestima, absència de normes i límits, manca d’informació, manca de comunicació, entre d’altres. També hi ha d’altres situacions socioculturals i característiques individuals que fan que se’n redueixi la possibilitat de consum, aquests serien els anomenats factors de protecció com són l’economia, tenir aficions, disposar d’adults de referència, etc. Conèixer i comprendre aquests factors és fonamental per poder realitzar un abordatge educatiu i preventiu basat en la reducció de riscos i en la responsabilitat i l’autonomia de les persones usuàries de drogues.

Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamics

Rationale Mephedrone (4-methylmethcathinone) is a still poorly known drug of abuse, alternative to ecstasy or cocaine. Objective The major aims were to investigate the pharmacokineticsa and locomotor activity of mephedrone in rats and provide a pharmacokinetic/pharmacodynamic model. Methods Mephedrone was administered to male SpragueDawley rats intravenously (10 mg/kg) and orally (30 and 60 mg/kg). Plasma concentrations and metabolites were characterized using LC/MS and LC-MS/MS fragmentation patterns. Locomotor activity was monitored for 180240 min. Results Mephedrone plasma concentrations after i.v. administration fit a two-compartment model (α=10.23 h−1, β=1.86 h−1). After oral administration, peak mephedrone concentrations were achieved between 0.5 and 1 h and declined to undetectable levels at 9 h. The absolute bioavailability of mephedrone was about 10 % and the percentage of mephedrone protein binding was 21.59±3.67%. We have identified five phase I metabolites in rat blood after oral administration. The relationship between brain levels and free plasma concentration was 1.85±0.08. Mephedrone induced a dose-dependent increase in locomotor activity, which lasted up to 2 h. The pharmacokineticpharmacodynamic model successfully describes the relationship between mephedrone plasma concentrations and its psychostimulant effect. Conclusions We suggest a very important first-pass effect for mephedrone after oral administration and an easy access to the central nervous system. The model described might be useful in the estimation and prediction of the onset, magnitude,and time course of mephedrone pharmacodynamics as well as to design new animal models of mephedrone addiction and toxicity.

Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamics

Rationale Mephedrone (4-methylmethcathinone) is a still poorly known drug of abuse, alternative to ecstasy or cocaine. Objective The major aims were to investigate the pharmacokineticsa and locomotor activity of mephedrone in rats and provide a pharmacokinetic/pharmacodynamic model. Methods Mephedrone was administered to male Sprague-Dawley rats intravenously (10 mg/kg) and orally (30 and 60 mg/kg). Plasma concentrations and metabolites were characterized using LC/MS and LC-MS/MS fragmentation patterns. Locomotor activity was monitored for 180-240 min. Results Mephedrone plasma concentrations after i.v. administration fit a two-compartment model (α=10.23 h−1, β=1.86 h−1). After oral administration, peak mephedrone concentrations were achieved between 0.5 and 1 h and declined to undetectable levels at 9 h. The absolute bioavailability of mephedrone was about 10 % and the percentage of mephedrone protein binding was 21.59±3.67%. We have identified five phase I metabolites in rat blood after oral administration. The relationship between brain levels and free plasma concentration was 1.85±0.08. Mephedrone induced a dose-dependent increase in locomotor activity, which lasted up to 2 h. The pharmacokinetic-pharmacodynamic model successfully describes the relationship between mephedrone plasma concentrations and its psychostimulant effect. Conclusions We suggest a very important first-pass effect for mephedrone after oral administration and an easy access to the central nervous system. The model described might be useful in the estimation and prediction of the onset, magnitude,and time course of mephedrone pharmacodynamics as well as to design new animal models of mephedrone addiction and toxicity.

Repeated doses of methylone, a new drug of abuse, induce changes in serotonin and dopamine systems in the mouse

Rationale Methylone, a new drug of abuse sold as"bath salts' has similar effects to ecstasy or cocaine. Objective We have investigated changes in dopaminergic and serotoninergic markers, indicative of neuronal damage, induced by methylone in the frontal cortex, hippocampus and striatum of mice and according two different treatment schedules. Methods Methylone was given subcutaneously to male Swiss CD1 mice and at an ambient temperature of 26ºC. Treatment A: three doses of 25 mg/Kg at 3.5 h interval between doses for two consecutive days. Treatment B: four doses of 25 mg/Kg at 3 h interval in one day. Results Repeated methylone administration induced hyperthermia and a significant loss in body weight. Following treatment A, methylone induced transient dopaminergic (frontal cortex) and serotoninergic (hippocampus) impairment. Following treatment B, transient dopaminergic (frontal cortex) and serotonergic (frontal cortex and hippocampus) changes 7 days after treatment were found. We found evidence of astrogliosis in the CA1 and the dentate gyrus of the hippocampus following treatment B. The animals also showed an increase in immobility time in the forced swim test, pointing to a depressive-like behavior. In cultured cortical neurons, methylone (for 24 and 48 h) did not induce a remarkable cytotoxic effect. Conclusions The neural effects of methylone differ depending upon the treatment schedule. Neurochemical changes elicited by methylone are apparent when administered at an elevated ambient temperature, four times per day at 3 h intervals, which is in accordance with its short half-life.

Seguimiento de dependientes del alcohol y/o de la cocaina despues de su salida de una Comunidad Terapeutica: estudio piloto

Introducción Los avances en farmacoterapia del alcoholismo podrían propiciar un cambio de paradigma, basado en los nuevos programas de reducción del consumo de alcohol. Material y Método Este estudio revisa los fundamentos neurobiológicos y farmacoterapéuticos del alcoholismo, centrándose en los antagonistas opioides, el tratamiento orientado a la abstinencia y el orientado hacia la reducción del consumo de alcohol. Resultados 1. Los programas de tratamiento de la dependencia del alcohol presentan sólo una eficacia pequeña o moderada. 2. Los pacientes presentan una elevada motivación para reducir el consumo de alcohol pero una baja motivación para abandonar de manera continuada al consumo de alcohol. 3. El programa de reducción continuada del consumo de alcohol, asociado a un tratamiento intermitente con naltrexona, puede ser de utilidad en los pacientes con una baja gravedad de la dependencia del alcohol. Discusión Aunque los pacientes que presentan una grave dependencia del alcohol deberían ser tratados en programas orientados hacia la abstención continuada, los que presentan una baja gravedad pueden beneficiarse de los programas de reducción del consumo de alcohol, los cuales pueden conseguir a corto plazo una reducción el número de consumiciones por día de consumo y, a largo plazo, incluso una progresiva reducción de la"obsesión" por beber, la conducta de búsqueda de alcohol y los trastornos médicos, conductuales y sociales, causados por el consumo excesivo de alcohol. Para poder llevar a cabo este cambio de paradigma en el tratamiento del alcoholismo, se requieren futuros ensayos clínicos controlados para evaluar su eficacia y su tolerabilidad.