Decreased hyperlocomotion induced by MK-801, but not amphetamine and caffeine in mice lacking cellular prion protein (PrP(C))

Brain Res Mol Brain Res. 2002 Nov 15;107(2):190-4. doi: 10.1016/s0169-328x(02)00526-0.

Abstract

The cellular prion protein (PrP(C)) has been involved in several neurodegenerative disorders however it has been proposed that it is also be implicated in psychotic disorders. We investigated the effect of three psychotropic drugs in locomotor activity of PrP(C) knockout (Prnp(O/O)) and wild-type mice. The NMDA receptor channel blocker MK-801 (0.25 mg/kg), the indirect dopamine agonist amphetamine (1 mg/kg) and the adenosine receptor antagonist caffeine (10 mg/kg) were administered i.p. after 60 min of habituation and locomotion was monitored for 3 h. Prnp(O/O) mice presented a diminished hyperlocomotor response to MK-801 treatment but normal response to amphetamine and caffeine compared to wild type mice. These results suggest that lack of PrP(C) leads to a functional alteration in the glutamatergic system, whereas the regulation of both dopaminergic and adenosinergic systems are preserved. Finally, lack of PrP(C) seems not to exacerbate the response to these psychotropic drugs, which modulate neurotransmitter systems possibly involved in schizophrenia and psychotic disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphetamine / pharmacology
  • Animals
  • Caffeine / pharmacology
  • Dizocilpine Maleate / pharmacology
  • Dopamine Agonists / pharmacology
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Excitatory Amino Acid Antagonists / pharmacology
  • Female
  • Hyperkinesis / chemically induced
  • Hyperkinesis / genetics
  • Hyperkinesis / metabolism
  • Male
  • Mental Disorders / genetics
  • Mental Disorders / metabolism*
  • Mental Disorders / physiopathology
  • Mice
  • Mice, Knockout
  • Motor Activity / drug effects
  • Motor Activity / genetics
  • PrPC Proteins / deficiency*
  • PrPC Proteins / genetics
  • Receptors, Dopamine / drug effects
  • Receptors, Dopamine / metabolism*
  • Receptors, Glutamate / drug effects
  • Receptors, Glutamate / metabolism*
  • Receptors, Purinergic P1 / drug effects
  • Receptors, Purinergic P1 / metabolism*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / genetics*

Substances

  • Dopamine Agonists
  • Excitatory Amino Acid Antagonists
  • PrPC Proteins
  • Receptors, Dopamine
  • Receptors, Glutamate
  • Receptors, Purinergic P1
  • Caffeine
  • Dizocilpine Maleate
  • Amphetamine