title: Sex Differences in Regional Brain Glucose Metabolism Following Opioid Withdrawal and Replacement.
abstract: 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, using18FDG 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.
authors.affiliation: Center for Neurosciences, Laboratory for Molecular and Behavioral Neuroimaging, Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors.forename: Giovanni C
authors.initials: GC
authors.lastname: Santoro
authors.affiliation: Center for Neurosciences, Laboratory for Molecular and Behavioral Neuroimaging, Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Carrion
authors.affiliation: Center for Neurosciences, Laboratory for Molecular and Behavioral Neuroimaging, Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors.forename: Krishna
authors.initials: K
authors.lastname: Patel
authors.affiliation: Center for Neurosciences, Laboratory for Molecular and Behavioral Neuroimaging, Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors.forename: Crystal
authors.initials: C
authors.lastname: Vilchez
authors.affiliation: Center for Neurosciences, Laboratory for Molecular and Behavioral Neuroimaging, Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Veith
authors.affiliation: Psychiatry Department, New York University School of Medicine, New York, NY, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Brodie
authors.affiliation: Center for Neurosciences, Laboratory for Molecular and Behavioral Neuroimaging, Feinstein Institute for Medical Research, Manhasset, NY, USA.|Psychiatry Department, New York University School of Medicine, New York, NY, USA.|Department of Molecular Medicine, Hofstra Northwell School of Medicine, Hempstead, NY, USA.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Dewey
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D001931:Brain Mapping; D002047:Buprenorphine / Q000494:pharmacology; D003430:Cross-Sectional Studies; D004195:Disease Models, Animal; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D008137:Longitudinal Studies; D008297:Male; D008691:Methadone / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology; D009021:Morphine Dependence / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D002047:Buprenorphine; D009020:Morphine; D005947:Glucose; D008691:Methadone