title: The role of dopamine and AMPA/kainate receptors in the nucleus accumbens in the hypermotility response to MK801.
abstract: The purpose of this study was to evaluate the role of endogenous dopamine in the hypermotility response to MK801. The administration of MK801 (0.1 mg/kg, SC) to rats produced an intense stimulation of coordinated locomotor activity, which was not associated with stereotyped behavior. This stimulatory response was inhibited by pretreatment with either reserpine (5 mg/kg, IP) or alpha-methyl-p-tyrosine (2 doses of 250 mg/kg, IP). Similarly, pretreatment with the D2 antagonist eticlopride (0.03 mg/kg, SC) or the D1 antagonist SCH23390 (0.1 mg/kg, SC) produced a marked inhibition of MK801-stimulated hypermotility, and the combination of eticlopride (0.03 mg/kg, SC) and SCH23390 (0.03 mg/kg, SC) produced a greater inhibition of MK801-stimulated locomotion than either agent alone. The administration of SCH23390 or eticlopride directly into the nucleus accumbens inhibited the locomotor response to MK801, with the combination of both drugs producing a greater inhibition than either agent alone. The intra-accumbens administration of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate receptor antagonists DNQX or GAMS also inhibited the locomotor response produced by MK801. These data suggest that the activation of D1 and D2 dopaminergic receptors and AMPA/kainate excitatory amino acid receptors in the nucleus accumbens is required for the stimulation of locomotor activity produced by MK801.
authors.affiliation: Division of Pharmacology, College of Pharmacy, Ohio State University, Columbus 43210.
authors.forename: D L
authors.initials: DL
authors.lastname: Willins
authors.forename: S
authors.initials: S
authors.lastname: Narayanan
authors.forename: L J
authors.initials: LJ
authors.lastname: Wallace
authors.forename: N J
authors.initials: NJ
authors.lastname: Uretsky
mesh_terms: D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology*; D065127:Dopamine D2 Receptor Antagonists; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000033:anatomy & histology / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D012110:Reserpine / Q000494:pharmacology; D019805:alpha-Methyltyrosine
chemical_list: D016291:Dizocilpine Maleate; D004298:Dopamine; D065127:Dopamine D2 Receptor Antagonists; D008781:Methyltyrosines; D018091:Receptors, AMPA; D017447:Receptors, Dopamine D1; D018092:Kainic Acid Receptors; D012110:Reserpine; D019805:alpha-Methyltyrosine