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Sensorimotor gating impairments induced by MK-801 treatment may be reduced by tolerance effect and by familiarization in monkeys.

Saletti PG, Maior RS, Hori E, Nishijo H, Tomaz C - Front Pharmacol (2015)

Bottom Line: Dizocilpine (MK-801) is a non-competitive NMDA antagonist that induces schizophreniclike effects.In order to evaluate MK-801 effects on monkeys' PPI, we tested eight capuchin monkeys (Sapajus spp.) using three different doses of MK-801 (0.01; 0.02; 0.03 mg/kg).Results show PPI impairment in acute administration of the highest dose (0.03 mg/kg).

View Article: PubMed Central - PubMed

Affiliation: Primate Center and Laboratory of Neurosciences and Behavior, Department of Physiological Sciences, Institute of Biology, University of Brasilia , Brasilia, Brazil.

ABSTRACT
Dizocilpine (MK-801) is a non-competitive NMDA antagonist that induces schizophreniclike effects. It is therefore widely used in experimental models of schizophrenia including prepulse inhibition (PPI) impairments in rodents. Nevertheless, MK-801 has never been tested in monkeys on a PPI paradigm. In order to evaluate MK-801 effects on monkeys' PPI, we tested eight capuchin monkeys (Sapajus spp.) using three different doses of MK-801 (0.01; 0.02; 0.03 mg/kg). Results show PPI impairment in acute administration of the highest dose (0.03 mg/kg). PPI impairment induced by MK-801 was reversed by re-exposure to the PPI test throughout treatment trials, in contrast with rodent studies. These results indicate that tolerance effect and familiarization with PPI test may reduce the sensorimotor gating deficits induced by MK-801 in monkeys, suggesting a drug-training interaction.

No MeSH data available.


Related in: MedlinePlus

MK-801 decreased startle response amplitude after administration of the higher dose (0.03 mg/kg) compared to VEH. Bars indicate startle response amplitude (mean ± SEM, n = 8) when presented pulse-alone trials (black bars) and prepulse+pulse trials (gray bars). *Indicates significant difference in pulse-alone trials between 0.03 mg/kg and VEH (p = 0.025) and 0.01 mg/kg (p = 0.014) in Friedman’s test.
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Figure 2: MK-801 decreased startle response amplitude after administration of the higher dose (0.03 mg/kg) compared to VEH. Bars indicate startle response amplitude (mean ± SEM, n = 8) when presented pulse-alone trials (black bars) and prepulse+pulse trials (gray bars). *Indicates significant difference in pulse-alone trials between 0.03 mg/kg and VEH (p = 0.025) and 0.01 mg/kg (p = 0.014) in Friedman’s test.

Mentions: In Figure 2, we show the mean startle response amplitude when pulse-alone and prepulse+pulse are considered separately, again regardless of experimental group. In pulse-alone situation, startle response differs only from VEH at the dose of 0.03 mg/kg (X2 = 5.000; p = 0.025, n = 8). In prepulse+pulse stimuli, no dose was statistically different from VEH (X2 = 7.738; p = 0.052, n = 8).


Sensorimotor gating impairments induced by MK-801 treatment may be reduced by tolerance effect and by familiarization in monkeys.

Saletti PG, Maior RS, Hori E, Nishijo H, Tomaz C - Front Pharmacol (2015)

MK-801 decreased startle response amplitude after administration of the higher dose (0.03 mg/kg) compared to VEH. Bars indicate startle response amplitude (mean ± SEM, n = 8) when presented pulse-alone trials (black bars) and prepulse+pulse trials (gray bars). *Indicates significant difference in pulse-alone trials between 0.03 mg/kg and VEH (p = 0.025) and 0.01 mg/kg (p = 0.014) in Friedman’s test.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4585034&req=5

Figure 2: MK-801 decreased startle response amplitude after administration of the higher dose (0.03 mg/kg) compared to VEH. Bars indicate startle response amplitude (mean ± SEM, n = 8) when presented pulse-alone trials (black bars) and prepulse+pulse trials (gray bars). *Indicates significant difference in pulse-alone trials between 0.03 mg/kg and VEH (p = 0.025) and 0.01 mg/kg (p = 0.014) in Friedman’s test.
Mentions: In Figure 2, we show the mean startle response amplitude when pulse-alone and prepulse+pulse are considered separately, again regardless of experimental group. In pulse-alone situation, startle response differs only from VEH at the dose of 0.03 mg/kg (X2 = 5.000; p = 0.025, n = 8). In prepulse+pulse stimuli, no dose was statistically different from VEH (X2 = 7.738; p = 0.052, n = 8).

Bottom Line: Dizocilpine (MK-801) is a non-competitive NMDA antagonist that induces schizophreniclike effects.In order to evaluate MK-801 effects on monkeys' PPI, we tested eight capuchin monkeys (Sapajus spp.) using three different doses of MK-801 (0.01; 0.02; 0.03 mg/kg).Results show PPI impairment in acute administration of the highest dose (0.03 mg/kg).

View Article: PubMed Central - PubMed

Affiliation: Primate Center and Laboratory of Neurosciences and Behavior, Department of Physiological Sciences, Institute of Biology, University of Brasilia , Brasilia, Brazil.

ABSTRACT
Dizocilpine (MK-801) is a non-competitive NMDA antagonist that induces schizophreniclike effects. It is therefore widely used in experimental models of schizophrenia including prepulse inhibition (PPI) impairments in rodents. Nevertheless, MK-801 has never been tested in monkeys on a PPI paradigm. In order to evaluate MK-801 effects on monkeys' PPI, we tested eight capuchin monkeys (Sapajus spp.) using three different doses of MK-801 (0.01; 0.02; 0.03 mg/kg). Results show PPI impairment in acute administration of the highest dose (0.03 mg/kg). PPI impairment induced by MK-801 was reversed by re-exposure to the PPI test throughout treatment trials, in contrast with rodent studies. These results indicate that tolerance effect and familiarization with PPI test may reduce the sensorimotor gating deficits induced by MK-801 in monkeys, suggesting a drug-training interaction.

No MeSH data available.


Related in: MedlinePlus