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

Adriana S Coitinho; Marcelo O Dietrich; Anselmo Hoffmann; Oscar P Dall'Igna; Diogo O Souza; Vilma R Martins; Ricardo R Brentani; Ivan Izquierdo; Diogo R Lara

doi:10.1016/s0169-328x(02)00526-0

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.

Authors

Adriana S Coitinho¹, Marcelo O Dietrich, Anselmo Hoffmann, Oscar P Dall'Igna, Diogo O Souza, Vilma R Martins, Ricardo R Brentani, Ivan Izquierdo, Diogo R Lara

Affiliation

¹ Departamento de Bioquímica, ICBS, UFRGS, Porto Alegre, Brazil. acoitinho@yahoo.com

PMID: 12425947
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