Reversal of dizocilpine-induced disruption of prepulse inhibition of an acoustic startle response by the 5-HT2 receptor antagonist ketanserin

Eur J Pharmacol. 1995 Dec 12;287(2):201-5. doi: 10.1016/0014-2999(95)00660-5.

Abstract

Prepulse inhibition can be reliably disrupted by non-competitive NMDA receptor antagonists such as dizocilpine. In recent study, we found that the potent D2/5-HT2 receptor antagonist, risperidone, but not the selective dopamine D2 receptor antagonist, raclopride, could reverse this disruption. The present study was therefore designed to examine the effect of the 5-HT2 receptor antagonist, ketanserin, against a dizocilpine-induced disruption of prepulse inhibition, as well as the behavioural stereotypy produced by this drug. Ketanserin (2 mg/kg) reversed the prepulse inhibition disruption produced by dizocilpine (0.15 mg/kg), as did the non-selective 5-HT1/5-HT2 receptor antagonist metergoline (1 mg/kg). Both drugs also attenuated some components of the behavioural stereotypy syndrome produced by dizocilpine (0.15 mg/kg). The present studies therefore suggest an interaction between 5-HT2 receptors and glutamatergic systems. This may be important for the antipsychotic profile of drugs having antagonist activity at 5-HT2 receptors.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Dizocilpine Maleate / pharmacology*
  • Ketanserin / pharmacology*
  • Locomotion / drug effects*
  • Male
  • Metergoline / pharmacology
  • Rats
  • Rats, Wistar
  • Reflex, Startle / drug effects*
  • Risperidone / pharmacology
  • Time Factors

Substances

  • Metergoline
  • Dizocilpine Maleate
  • Ketanserin
  • Risperidone