Matthew R Holahan1, Melanie J Clarke, Delaney D Hines. 1. Department of Psychology, Institute of Neuroscience, Carleton University, 1125 Colonel By Drive, 337 Life Science Research Building, Ottawa, ON, K1S 5B6, Canada. matthew_holahan@carleton.ca
Abstract
RATIONALE: The current study examined the effect of the noncompetitive N-methyl-D: -aspartate (NMDA) receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) on the extinction of food-based operant responding. OBJECTIVES: Experiments were carried out to determine (1) the nature of the elevated responding when rats were under the influence of MK-801, (2) the effect of combined and separate D1- and D2-like dopaminergic antagonists (SCH 23390 and haloperidol) on this MK-801-induced behavioral effect and (3) the neural correlates on and off MK-801 using immunohistochemical localization of the phosphorylated forms of the extracellular signal-regulated kinase-1 and -2. METHODS: Male Long Evans rats were trained using operant conditioning procedures then treated with the various compounds, and resultant extinction pressing was measured. RESULTS: A moderate dose (0.1 mg/kg) of MK-801 produced a persistent, elevated lever pressing throughout the entire 30-min extinction session. When animals were pretreated with combined or separate dopamine (DA) D1- or D2-like receptor antagonists, extinction responding under MK-801 was significantly reduced. Examination of pERK1/2 labeling in MK-801-treated animals showed reduced staining in the infralimbic and piriform cortices and elevated staining in the nucleus accumbens compared with controls. CONCLUSIONS: These data show that MK-801 elevates food-based extinction behavior that can be reduced by DA receptor antagonists. The disrupted extinction behavior may be mediated, in part, by disinhibition of corticostriatal circuits.
RATIONALE: The current study examined the effect of the noncompetitive N-methyl-D: -aspartate (NMDA) receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) on the extinction of food-based operant responding. OBJECTIVES: Experiments were carried out to determine (1) the nature of the elevated responding when rats were under the influence of MK-801, (2) the effect of combined and separate D1- and D2-like dopaminergic antagonists (SCH 23390 and haloperidol) on this MK-801-induced behavioral effect and (3) the neural correlates on and off MK-801 using immunohistochemical localization of the phosphorylated forms of the extracellular signal-regulated kinase-1 and -2. METHODS: Male Long Evans rats were trained using operant conditioning procedures then treated with the various compounds, and resultant extinction pressing was measured. RESULTS: A moderate dose (0.1 mg/kg) of MK-801 produced a persistent, elevated lever pressing throughout the entire 30-min extinction session. When animals were pretreated with combined or separate dopamine (DA) D1- or D2-like receptor antagonists, extinction responding under MK-801 was significantly reduced. Examination of pERK1/2 labeling in MK-801-treated animals showed reduced staining in the infralimbic and piriform cortices and elevated staining in the nucleus accumbens compared with controls. CONCLUSIONS: These data show that MK-801 elevates food-based extinction behavior that can be reduced by DA receptor antagonists. The disrupted extinction behavior may be mediated, in part, by disinhibition of corticostriatal circuits.
Authors: Matthew J Horchar; Joy L Kappesser; Maria R Broderick; Makayla R Wright; Justin R Yates Journal: Drug Alcohol Depend Date: 2022-02-12 Impact factor: 4.492