title: Cocaine differentially affects synaptic activity in memory and midbrain areas of female and male rats: an in vivo MEMRI study.
abstract: Manganese enhanced magnetic resonance imaging (MEMRI) has been previously used to determine the effect of acute cocaine on calcium-dependent synaptic activity in male rats. However, there have been no MEMRI studies examining sex differences in the functional neural circuits affected by repeated cocaine. In the present study, we used MEMRI to investigate the effects of repeated cocaine on brain activation in female and male rats. Adult female and male rats were scanned at 4.7 Tesla three days after final treatment with saline, a single cocaine injection (15 mg kg-1, i.p. × 1 day) or repeated cocaine injections (15 mg kg-1, i.p. × 10 days). A day before imaging rats were provided with an i.p. injection of manganese chloride (70 mg kg-1). Cocaine produced effects on MEMRI activity that were dependent on sex. In females, we observed that a single cocaine injection reduced MEMRI activity in hippocampal CA3, ventral tegmental area (VTA), and median Raphé, whereas repeated cocaine increased MEMRI activity in dentate gyrus and interpeduncular nucleus. In males, repeated cocaine reduced MEMRI activity in VTA. Overall, it appeared that female rats showed a general trend towards increase MEMRI activity with single cocaine and reduced activity with repeated exposure, while male rats showed a trend towards opposite effects. Our results provide evidence for sex differences in the in vivo neural response to cocaine, which involves primarily hippocampal, amygdala and midbrain areas.
authors.affiliation: Department of Psychiatry, McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, FL, 32610, USA.
authors.forename: Pablo D
authors.initials: PD
authors.lastname: Perez
authors.affiliation: Department of Psychiatry, McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, FL, 32610, USA.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Hall
authors.affiliation: Department of Physiological Sciences, College of Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: Jasenka
authors.initials: J
authors.lastname: Zubcevic
authors.affiliation: Department of Psychiatry, McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, FL, 32610, USA. febo@ufl.edu.|Center for Addiction Research and Education (CARE), University of Florida, Gainesville, FL, USA. febo@ufl.edu.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Febo
mesh_terms: D000818:Animals; D002712:Chlorides; D003042:Cocaine / Q000008:administration & dosage*; D003287:Contrast Media; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005260:Female; D008279:Magnetic Resonance Imaging; D008297:Male; D017895:Manganese Compounds; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D008636:Mesencephalon / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D020318:Rats, Long-Evans; D012727:Sex Characteristics; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology
chemical_list: D002712:Chlorides; D003287:Contrast Media; D018765:Dopamine Uptake Inhibitors; D017895:Manganese Compounds; D003042:Cocaine; C025340:manganese chloride
keywords: Addiction; Cocaine; MEMRI; Manganese; Sex differences; Synaptic activity