TY - JOUR
T1 - Time course of prepulse inhibition disruption induced by dopamine agonists and NMDA antagonists
T2 - Effects of drug administration regimen
AU - Li, Ming
AU - He, Wei
AU - Chen, Jing
N1 - Funding Information:
We thank Professor Ronald Hammer Jr. for the help on PPI procedure. We also thank Mr. Tao Sun for his technical support and Ms. Heidi Gonzalez for her editorial work. This study was funded in part by a support from the Nebraska Tobacco Settlement Biomedical Research Development Funds , and by a research grant ( 07R-1775 ) from the Stanley Medical Research Institute to ML.
PY - 2011/9
Y1 - 2011/9
N2 - Prepulse inhibition (PPI) of acoustic startle response is impaired in patients with schizophrenia and in animals acutely treated with dopamine agonists and NMDA antagonists. In this study, we investigated the time course of PPI disruption induced by repeated amphetamine, quinpirole, phencyclidine (PCP), and dizocilpine (MK-801) treatment. We focused on how PPI disruption development was influenced by drug administration regimens, comparing a constant versus an escalating dosing regimen. Male Sprague-Dawley rats were repeatedly treated with amphetamine (1.25-5.0 mg/kg, or constant 5.0 mg/kg, sc), PCP (0.50-2.0 mg/kg, or constant 0.5, 1.0 or 2.0 mg/kg, sc), quinpirole (0.03-0.12 mg/kg, or constant 0.12 mg/kg, sc), MK-801 (0.025-0.10 mg/kg, or constant 0.10 mg/kg, sc) or vehicle (saline) and tested for PPI once daily for 6 consecutive days. When amphetamine 5.0 mg/kg or quinpirole 0.12 mg/kg was administrated on a constant dosing schedule, both drugs disrupted PPI upon acute administration, but had no effect after repeated treatment and testing (days 2-5). However, when amphetamine 5.0 mg/kg or quinpirole 0.12 mg/kg was preceded by two lower doses in an escalating dosing regimen, both drugs still disrupted PPI on days 5 and 6 when the constant amphetamine and quinpirole had no effect. For PCP and MK-801, repeated treatment under both regimens produced a stable and persistent disruption of PPI. Startle magnitude increased progressively and dose-dependently under both regimens for all drugs except for quinpirole, which caused a decrease. These results suggest that the drug dosing schedule, rather than the absolute amount of drug that an animal receives, has a greater impact on the development of PPI-disruptive effect of dopamine agonists than NMDA antagonists. Thus, in order to mimic the emerging process of PPI deficit with dopamine agonists, an escalating dosing regimen should be used.
AB - Prepulse inhibition (PPI) of acoustic startle response is impaired in patients with schizophrenia and in animals acutely treated with dopamine agonists and NMDA antagonists. In this study, we investigated the time course of PPI disruption induced by repeated amphetamine, quinpirole, phencyclidine (PCP), and dizocilpine (MK-801) treatment. We focused on how PPI disruption development was influenced by drug administration regimens, comparing a constant versus an escalating dosing regimen. Male Sprague-Dawley rats were repeatedly treated with amphetamine (1.25-5.0 mg/kg, or constant 5.0 mg/kg, sc), PCP (0.50-2.0 mg/kg, or constant 0.5, 1.0 or 2.0 mg/kg, sc), quinpirole (0.03-0.12 mg/kg, or constant 0.12 mg/kg, sc), MK-801 (0.025-0.10 mg/kg, or constant 0.10 mg/kg, sc) or vehicle (saline) and tested for PPI once daily for 6 consecutive days. When amphetamine 5.0 mg/kg or quinpirole 0.12 mg/kg was administrated on a constant dosing schedule, both drugs disrupted PPI upon acute administration, but had no effect after repeated treatment and testing (days 2-5). However, when amphetamine 5.0 mg/kg or quinpirole 0.12 mg/kg was preceded by two lower doses in an escalating dosing regimen, both drugs still disrupted PPI on days 5 and 6 when the constant amphetamine and quinpirole had no effect. For PCP and MK-801, repeated treatment under both regimens produced a stable and persistent disruption of PPI. Startle magnitude increased progressively and dose-dependently under both regimens for all drugs except for quinpirole, which caused a decrease. These results suggest that the drug dosing schedule, rather than the absolute amount of drug that an animal receives, has a greater impact on the development of PPI-disruptive effect of dopamine agonists than NMDA antagonists. Thus, in order to mimic the emerging process of PPI deficit with dopamine agonists, an escalating dosing regimen should be used.
KW - Dizocilpine (MK-801)
KW - Prepulse inhibition of acoustic startle
KW - Quinpirole
KW - Repeated amphetamine treatment
KW - Repeated phencyclidine treatment
KW - Sensitization effect
KW - Tolerance effect
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U2 - 10.1016/j.pbb.2011.05.001
DO - 10.1016/j.pbb.2011.05.001
M3 - Article
C2 - 21600239
AN - SCOPUS:79959840031
VL - 99
SP - 509
EP - 518
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
SN - 0091-3057
IS - 3
ER -