RESUMEN
Adulteration is a common practice in the illicit drugs market, but the psychoactive and toxic effects provided by adulterants are clinically underestimated. Coca-paste (CP) is a smokable form of cocaine which has an extremely high abuse liability. CP seized samples are sold adulterated; however, qualitative and quantitative data of CP adulteration in forensic literature is still scarce. Besides, it is unknown if adulterants remain stable when CP is heated. This study was designed to report the chemical content of an extensive series of CP seized samples and to demonstrate the stability (i.e., chemical integrity) of the adulterants heated. To achieve this goal, the following strategies were applied: (1) a CP adulterated sample was heated and its fume was chemically analyzed; (2) the vapor of isolated adulterants were analyzed after heating; (3) plasma levels of animals exposed to CP and adulterants were measured. Ninety percent of CP seized samples were adulterated. Adulteration was dominated by phenacetin and caffeine and much less by other compounds (i.e., aminopyrine, levamisole, benzocaine). In the majority of CP analyzed samples, both cocaine and caffeine content was 30%, phenacetin 20% and the combination of these three components reached 90%. Typical cocaine pyrolysis compounds (i.e., BA, CMCHTs, and AEME) were observed in the volatilized cocaine and CP sample but no pyrolysis compounds were found after isolated adulterants heating. Cocaine, phenacetin, and caffeine were detected in plasma. We provide current forensic data about CP seized samples and demonstrated the chemical integrity of their adulterants heated.
Asunto(s)
Anestésicos Locales/análisis , Anestésicos Locales/química , Coca/química , Cocaína/análisis , Cocaína/química , Drogas Ilícitas/análisis , Animales , Cafeína/análisis , Cafeína/química , Cromatografía Líquida de Alta Presión , Coca/metabolismo , Cocaína/sangre , Contaminación de Medicamentos , Cromatografía de Gases y Espectrometría de Masas , Drogas Ilícitas/sangre , Drogas Ilícitas/química , Masculino , Fenacetina/análisis , Fenacetina/sangre , Fenacetina/química , Ratas , Ratas WistarRESUMEN
Oral, intraperitoneal, or intravenous have been the common routes of administration used to study the behavioral and neurochemical pharmacology of caffeine, one of the most widely used psychoactive substances worldwide. We have reported that caffeine is an active adulterant frequently found in coca-paste (CP)-seized samples, a highly addictive form of smokable cocaine. The role of caffeine in the psychostimulant and neurochemical effects induced by CP remains under study. No preclinical animal studies have been performed so far to characterize the effects of caffeine when it is administered through the pulmonary inhalation route. Caffeine (10, 25, and 50 mg) was volatilized and rats were exposed to one inhalation session of its vapor. The stimulant effect was automatically recorded and plasmatic levels of caffeine were measured. Caffeine capability (50 mg) to increase extracellular dopamine (DA) levels in nucleus accumbens shell was also studied by in vivo microdialysis in non-anesthetized animals. A dose-dependent stimulant effect induced by volatilized caffeine was observed and this effect was directly related with caffeine plasmatic levels. A significant increase in the extracellular DA was achieved after 50 mg of volatilized caffeine exposure. This is the first report showing pharmacological acute effects of caffeine through the pulmonary inhalation route of administration and suggests that this could be a condition under which caffeine can elevate its weak reinforcing effect and even enhance the psychostimulant effect and abuse liability of smokable adulterated psychostimulant drugs.
Asunto(s)
Cafeína/administración & dosificación , Estimulantes del Sistema Nervioso Central/administración & dosificación , Dopaminérgicos/administración & dosificación , Dopamina/metabolismo , Núcleo Accumbens/efectos de los fármacos , Núcleo Accumbens/metabolismo , Administración por Inhalación , Animales , Cafeína/sangre , Cafeína/química , Estimulantes del Sistema Nervioso Central/sangre , Estimulantes del Sistema Nervioso Central/química , Trastornos Relacionados con Cocaína/metabolismo , Dopaminérgicos/sangre , Dopaminérgicos/química , Relación Dosis-Respuesta a Droga , Conducta Exploratoria/efectos de los fármacos , Masculino , Modelos Animales , Actividad Motora/efectos de los fármacos , Ratas Wistar , VolatilizaciónRESUMEN
RATIONALE: Caffeine is one of the psychoactive substances most widely used as an adulterant in illicit drugs, such as cocaine. Animal studies have demonstrated that caffeine is able to potentiate several cocaine actions, although the enhancement of the cocaine reinforcing property by caffeine is less reported, and the results depend on the paradigms and experimental protocols used. OBJECTIVES: We examined the ability of caffeine to enhance the motivational and rewarding properties of cocaine using an intravenous self-administration paradigm in rats. Additionally, the role of caffeine as a primer cue during extinction was evaluated. METHODS: In naïve rats, we assessed (1) the ability of the cocaine (0.250-0.125 mg/kg/infusion) and caffeine (0.125-0.0625 mg/kg/infusion) combination to maintain self-administration in fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement compared with cocaine or caffeine alone and (2) the effect of caffeine (0.0625 mg/kg/infusion) in the maintenance of responding in the animals exposed to the combination of the drugs during cocaine extinction. RESULTS: Cocaine combined with caffeine and cocaine alone was self-administered on FR and PR schedules of reinforcement. Interestingly, the breaking point determined for the cocaine + caffeine group was significantly higher than the cocaine group. Moreover, caffeine, that by itself did not maintain self-administration behavior in naïve rats, maintained drug-seeking behavior of rats previously exposed to combinations of cocaine + caffeine. CONCLUSIONS: Caffeine enhances the reinforcing effects of cocaine and its motivational value. Our results highlight the role of active adulterants commonly used in cocaine-based illicit street drugs.
Asunto(s)
Cafeína/farmacología , Estimulantes del Sistema Nervioso Central/farmacología , Cocaína/administración & dosificación , Condicionamiento Operante , Inhibidores de Captación de Dopamina/administración & dosificación , Comportamiento de Búsqueda de Drogas/efectos de los fármacos , Motivación/efectos de los fármacos , Recompensa , Animales , Masculino , Ratas , Ratas Sprague-Dawley , Esquema de Refuerzo , Refuerzo en Psicología , AutoadministraciónRESUMEN
Neonatal handling has an impact on adult behavior of experimental animals and is associated with rapid and increased palatable food ingestion, impaired behavioral flexibility, and fearless behavior to novel environments. These symptoms are characteristic features of impulsive trait, being controlled by the medial prefrontal cortex (mPFC). Impulsive behavior is a key component of many psychiatric disorders such as attention deficit hyperactivity disorder (ADHD), manic behavior, and schizophrenia. Others have reported a methylphenidate (MPH)-induced enhancement of mPFC functioning and improvements in behavioral core symptoms of ADHD patients. The aims of the present study were: (i) to find in vivo evidence for an association between neonatal handling and the development of impulsive behavior in adult Wistar rats and (ii) to test whether neonatal handling could have an impact on monoamine levels in the mPFC and the pharmacological response to MPH in vivo. Therefore, experimental animals (litters) were classified as: "non-handled" and "handled" (10[Formula: see text]min/day, postnatal days 1-10). After puberty, they were exposed to either a larger and delayed or smaller and immediate reward (tolerance to delay of reward task). Acute MPH (3[Formula: see text]mg/Kg. i.p.) was used to suppress and/or regulate impulsive behavior. Our results show that only neonatally handled male adult Wistar rats exhibit impulsive behavior with no significant differences in monoamine levels in the medial prefrontal cortex, together with a decreased response to MPH. On this basis, we postulate that early life interventions may have long-term effects on inhibitory control mechanisms and affect the later response to pharmacological agents during adulthood.
Asunto(s)
Estimulantes del Sistema Nervioso Central/farmacología , Manejo Psicológico , Conducta Impulsiva/efectos de los fármacos , Conducta Impulsiva/fisiología , Metilfenidato/farmacología , Factores de Edad , Análisis de Varianza , Animales , Animales Recién Nacidos , Monoaminas Biogénicas/metabolismo , Peso Corporal/efectos de los fármacos , Condicionamiento Operante , Modelos Animales de Enfermedad , Femenino , Masculino , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/metabolismo , Embarazo , Ratas , Ratas Wistar , Refuerzo en Psicología , Factores Sexuales , Factores de TiempoRESUMEN
BACKGROUND AND OBJECTIVES: Caffeine is an active adulterant found in several drugs of abuse including coca paste (CP). We had previously demonstrated that caffeine potentiated the acute stimulant effect induced by CP seized samples. The role of caffeine in the expression of sensitization elicited by a CP seized sample (CP1) was here evaluated. METHODS: CP1 (equivalent dose of 10 mg/kg of cocaine), cocaine (pure, 10 mg/kg), a combination of cocaine 10 mg/kg plus caffeine 2.5 mg/kg (CP1-surrogate) and saline (control) were intraperitoneally injected in male rats under two different sensitization schedules. Ambulatory locomotion was recorded in 58 animals. RESULTS: After five daily CP1 injections and 5 days of withdrawal, CP1-challenged animals displayed a more robust sensitization than cocaine-treated animals. When a 3 injections-regime of CP1-surrogate or cocaine was assayed, only CP1-surrogate was able to elicit sensitization. DISCUSSION AND CONCLUSIONS: Caffeine enhances and accelerates the CP1-induced sensitization. SCIENTIFIC SIGNIFICANCE: Results may shed light on the fast and high dependence observed in CP users.