title: Comparison of the MK-801-induced increase in non-rewarded appetitive responding with dopamine agonists and locomotor activity in rats.
abstract: Systemic administration of the noncompetitive N-methyl-D-aspartate (NMDA)- receptor antagonist, MK-801, has been proposed to model cognitive deficits similar to those seen in patients with schizophrenia. Evidence has shown that MK-801 increases the probability of operant responding during extinction, possibly modeling perseveration, as would be seen in patients with schizophrenia. This MK-801-induced behavioral perseveration is reversed by dopamine receptor antagonism. To further explore the role of dopamine in this behavioral change, the current study sought to determine if the MK-801-induced increase in non-rewarded operant responding could be mimicked by dopamine agonism and determine how it was related to locomotor activity. Male Long Evans rats were treated systemically with MK-801, cocaine, GBR12909 or apomorphine (APO) and given a single trial operant extinction session, followed by a separate assessment of locomotor activity. Both MK-801 (0.05 mg/kg) and cocaine (10 mg/kg) significantly increased responding during the extinction session and both increased horizontal locomotor activity. No dose of GBR-12909 (5, 10 or 20 mg/kg) was found to effect non-rewarded operant responding or locomotor activity. APO (0.05, 0.5, 2 or 5 mg/kg) treatment produced a dose-dependent decrease in both operant responding and locomotor activity. These results suggest the possibility that, rather than a primary influence of increased dopamine concentration on elevating bar-pressing responses during extinction, other neurotransmitter systems may be involved.
authors.affiliation: Department of Neuroscience, Carleton University, Ottawa, Canada.
authors.forename: Parnell L
authors.initials: PL
authors.lastname: Davis-MacNevin
authors.forename: Jordan
authors.initials: J
authors.lastname: Dekraker
authors.forename: Liane
authors.initials: L
authors.lastname: LaDouceur
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Holahan
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004298:Dopamine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D005108:Extinction, Psychological / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: C461261:(1-(2-(bis(4-fluorophenyl)methoxy)ethyl)-4-(3-hydroxy-3-phenylpropyl) piperazinyl decanoate); D018491:Dopamine Agonists; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D003042:Cocaine; D001058:Apomorphine; D004298:Dopamine
keywords: Apomorphine; NMDA-receptor antagonist; cocaine; dopamine; dopamine receptor; extinction; rats; responsiveness; schizophrenia