Differential effects of CGP 37849 and MK-801, competitive and noncompetitive NMDA antagonists, with respect to the modulation of sensorimotor gating and dopamine outflow in the prefrontal cortex of rats

Naunyn Schmiedebergs Arch Pharmacol. 1994 Nov;350(5):555-62. doi: 10.1007/BF00173026.

Abstract

In the present study we compared effects of the competitive and non-competitive NMDA antagonists CGP 37849 and MK-801, respectively, on sensorimotor gating in rats, measured as prepulse-induced inhibition of the acoustic startle response, and the outflow of dopamine in the rat prefrontal cortex. CGP 37849 (10, 20 mg/kg), decreased the amplitude of the acoustic startle response, but was without effect on the prepulse-induced inhibition of the acoustic startle response. MK-801 (0.4 but not 0.2 mg/kg) enhanced the amplitude of the acoustic startle response and its doses of 0.2 and 0.4 mg/kg markedly attenuated the prepulse-induced inhibition of the acoustic startle response. The effects of MK-801 (0.4 mg/kg) on the prepulse-induced inhibition of the acoustic startle response were not antagonized by the selective antagonists of D-2 and D-1 dopaminergic receptors, S(-)sulpiride (25 mg/kg) and SCH 23390 (0.1 mg/kg), respectively. When given alone, S(-)sulpiride attenuated the amplitude of the acoustic startle response and failed to altered the prepulse-induced inhibition of the acoustic startle response. SCH 23390 (0.1 mg/kg) failed to alter the amplitude and prepulse-induced inhibition of the acoustic startle response. The effects of CGP 37849 and MK-801 also differed with respect to dopamine outflow. MK-801 (0.2 and 0.4 mg/kg) enhanced the outflow of dopamine in the rat prefrontal cortex, while CGP 37849 (10 and 20 mg/kg) was without any effect on the extracellular concentration of dopamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Comparative Study

MeSH terms

  • 2-Amino-5-phosphonovalerate / analogs & derivatives*
  • 2-Amino-5-phosphonovalerate / pharmacology
  • Acoustic Stimulation
  • Animals
  • Benzazepines / pharmacology
  • Binding, Competitive
  • Dizocilpine Maleate / pharmacology*
  • Dopamine / metabolism*
  • Male
  • Phencyclidine / pharmacology
  • Prefrontal Cortex / drug effects*
  • Prefrontal Cortex / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Reflex, Startle / drug effects*
  • Sulpiride / pharmacology

Substances

  • Benzazepines
  • Receptors, N-Methyl-D-Aspartate
  • 2-amino-4-methyl-5-phosphono-3-pentenoic acid
  • Dizocilpine Maleate
  • 2-Amino-5-phosphonovalerate
  • Sulpiride
  • Phencyclidine
  • Dopamine