title: Estradiol facilitation of cocaine-induced locomotor sensitization in female rats requires activation of mGluR5.
abstract: In comparison to men, women exhibit enhanced responsiveness to the stimulating and addictive properties of cocaine. A growing body of evidence implicates the steroid hormone estradiol in mediating this sex difference, yet the mechanisms underlying estradiol enhancement of behavioral responses to cocaine in females are not known. Recently, we have found that estrogen receptor alpha (ERα) functionally couples with the metabotropic glutamate receptor 5 (mGluR5) to mediate the effects of estradiol on both cellular activation as well as dendritic spine plasticity in brain regions involved in cocaine-induced behavioral sensitization. Thus, we sought to determine whether mGluR5 activation is required for the facilitative effects of estradiol on locomotor responses to cocaine. To test this hypothesis, ovariectomized (OVX) female rats were tested for locomotor activity on the first and fifth days of daily systemic injections of cocaine. For the 2 days prior to each locomotor test, animals were injected with the mGluR5 antagonist MPEP (or vehicle) and estradiol (or oil). MPEP treatment blocked the facilitative effects of estradiol on cocaine-induced locomotor sensitization, without affecting acute responses to cocaine or the inhibitory actions of estradiol on weight gain. Considered together, these data indicate that mGluR5 activation is critical for the actions of estradiol on cocaine-induced behavioral sensitization.
authors.affiliation: Department of Neuroscience, University of Minnesota, 6-145 Jackson Hall, 321 Church St SE, Minneapolis, MN 55455, USA. Electronic address: lamartin@umn.edu.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Martinez
authors.affiliation: Department of Neuroscience, University of Minnesota, 6-145 Jackson Hall, 321 Church St SE, Minneapolis, MN 55455, USA; Graduate Program of Neuroscience, University of Minnesota, 6-145 Jackson Hall, 321 Church St SE, Minneapolis, MN 55455, USA.
authors.forename: Brittni M
authors.initials: BM
authors.lastname: Peterson
authors.affiliation: Department of Neuroscience, University of Minnesota, 6-145 Jackson Hall, 321 Church St SE, Minneapolis, MN 55455, USA; Graduate Program of Neuroscience, University of Minnesota, 6-145 Jackson Hall, 321 Church St SE, Minneapolis, MN 55455, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Meisel
authors.affiliation: Department of Neuroscience, University of Minnesota, 6-145 Jackson Hall, 321 Church St SE, Minneapolis, MN 55455, USA; Graduate Program of Neuroscience, University of Minnesota, 6-145 Jackson Hall, 321 Church St SE, Minneapolis, MN 55455, USA.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Mermelstein
mesh_terms: D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D008124:Locomotion / Q000187:drug effects*; D010052:Ovariectomy; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011931:Reactive Inhibition; D064529:Receptor, Metabotropic Glutamate 5 / Q000187:drug effects*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D018765:Dopamine Uptake Inhibitors; D004967:Estrogens; D018691:Excitatory Amino Acid Antagonists; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D004958:Estradiol; C121465:6-methyl-2-(phenylethynyl)pyridine; D003042:Cocaine
keywords: Behavioral sensitization; Drug addiction; Estrogen; Nucleus accumbens