RESUMEN
Methadone and buprenorphine are currently the most common pharmacological treatments for opioid dependence. Interestingly, the clinical response to these drugs appears to be sex specific. That is, females exhibit superior therapeutic efficacy, defined as extended periods of abstinence and longer time to relapse, compared with males. However, the underlying metabolic effects of opioid withdrawal and replacement have not been examined. Therefore, using 18FDG and microPET, we measured differences in regional brain glucose metabolism in males and females following morphine withdrawal and subsequent methadone or buprenorphine replacement. In both males and females, spontaneous opioid withdrawal altered glucose metabolism in regions associated with reward and drug dependence. Specifically, metabolic increases in the thalamus, as well as metabolic decreases in insular cortex and the periaqueductal gray, were noted. However, compared with males, females exhibited increased metabolism in the preoptic area, primary motor cortex, and the amygdala, and decreased metabolism in the caudate/putamen and medial geniculate nucleus. Methadone and buprenorphine initially abolished these changes uniformly, but subsequently produced their own regional metabolic alterations that varied by treatment and sex. Compared with sex-matched control animals undergoing spontaneous opioid withdrawal, male animals treated with methadone exhibited increased caudate/putamen metabolism, whereas buprenorphine produced increased ventral striatum and motor cortex metabolism in females, and increased ventral striatum and somatosensory cortex metabolism in males. Notably, when treatment effects were compared between sexes, methadone-treated females showed increased cingulate cortex metabolism, whereas buprenorphine-treated females showed decreased metabolism in cingulate cortex and increased metabolism in the globus pallidus. Perhaps the initial similarities in males and females underlie early therapeutic efficacy, whereas these posttreatment sex differences contribute to clinical treatment failure more commonly experienced by the former.
Asunto(s)
Encéfalo/metabolismo , Glucosa/metabolismo , Dependencia de Morfina/tratamiento farmacológico , Dependencia de Morfina/metabolismo , Caracteres Sexuales , Analgésicos Opioides/farmacología , Animales , Encéfalo/diagnóstico por imagen , Encéfalo/efectos de los fármacos , Mapeo Encefálico , Buprenorfina/farmacología , Estudios Transversales , Modelos Animales de Enfermedad , Femenino , Fluorodesoxiglucosa F18 , Estudios Longitudinales , Masculino , Metadona/farmacología , Morfina/farmacología , Dependencia de Morfina/diagnóstico por imagen , Tomografía de Emisión de Positrones , Radiofármacos , Ratas Sprague-Dawley , Resultado del TratamientoRESUMEN
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the authors. The authors have requested to retract this paper as the corresponding author had not sought the prior agreement of his co-authors to submit the paper for publication.
Asunto(s)
Estimulación Encefálica Profunda/métodos , Dependencia de Morfina/diagnóstico por imagen , Dependencia de Morfina/terapia , Núcleo Accumbens , Animales , Condicionamiento Operante/efectos de los fármacos , Medios de Contraste , Antagonistas del GABA/farmacología , Genes fos/efectos de los fármacos , Interneuronas/efectos de los fármacos , Imagen por Resonancia Magnética/métodos , Masculino , Manganeso , Dependencia de Morfina/psicología , Neuronas Aferentes/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Recurrencia , Ácido gamma-Aminobutírico/metabolismoRESUMEN
Over the last two decades, SPECT (single photon emission computed tomography) and especially PET (positron emission tomography) have proven increasingly effective imaging modalities in the study of human psychopharmacology. Abusing populations can be studied at multiple times after abstinence begins, to give information about neurochemical and physiological adaptations of the brain during recovery from addiction. Individual human subjects can be studied using multiple positron labeled radiotracers, so as to probe more than one facet of brain function. PET and SPECT have been used to help our understanding of many aspects of the pharmacokinetics and pharmacodynamics of abused drugs, and have made valuable contributions in terms of drug mechanisms, drug interactions (e.g. cocaine and alcohol) and drug toxicities. They have also been employed to study the acute effects of drugs on populations of active drug abusers and of normal controls, and to evaluate the neurochemical consequences of candidate therapies for drug abuse. A particularly productive strategy has been the use of PET in conjunction with neuropsychological testing of subjects, to allow correlation of imaging data with uniquely human aspects of the effects of drugs, such as euphoria and craving.