Effect of the protein kinase C inhibitor, staurosporine, on the high dose of methamphetamine-induced behavioral sensitization to dizocilpine (MK-801).
Psychopharmacology (Berl)
; 180(1): 100-6, 2005 Jun.
Article
en En
| MEDLINE
| ID: mdl-15682296
ABSTRACT
RATIONALE In our preliminary study, methamphetamine (METH) at 2.5 mg/kg, but not at 1.0 mg/kg, induced a delayed increase in glutamate levels in the nucleus accumbens (NAc). We hypothesize that repeated increases in glutamate levels produces behavioral sensitization to a selective uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, dizocilpine (MK-801), and that an activation of protein kinase C (PKC) plays an important role for this sensitization. OBJECTIVES:
This study was conducted to confirm delayed increases in glutamate levels induced by a higher dose of METH (2.5 mg/kg), and to examine the effect of straurosporine, a PKC inhibitor, on the higher dose of METH-induced sensitization to dizocilpine.METHODS:
The effects of METH on extracellular glutamate levels in the NAc were studied using in vivo microdialysis. Locomotor activity was measured by using an infrared sensor.RESULTS:
METH at 2.5 mg/kg, but not at 1.0 mg/kg, induced delayed increases in glutamate levels. The acute administration of staurosporine did not affect the locomotor activity by a single injection of METH (2.5 mg/kg). Repeated METH administrations (2.5 mg/kg, once in every other day, for five times) developed behavioral sensitization to the locomotion-inducing effect of dizocilpine (0.2 mg/kg), a selective uncompetitive NMDA receptor antagonist. Staurosporine (0.1 mg/kg), given 120 min later for every METH treatment, inhibited the development of behavioral sensitization to dizocilpine.CONCLUSIONS:
These results suggest the involvement of increased glutamate levels and an activation of PKC in delayed-induced synaptic and cellular plasticity underlying the higher dose of METH-induced behavioral sensitization to dizocilpine.
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Banco de datos:
MEDLINE
Asunto principal:
Proteína Quinasa C
/
Maleato de Dizocilpina
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Antagonistas de Aminoácidos Excitadores
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Estaurosporina
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Inhibidores Enzimáticos
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Estimulantes del Sistema Nervioso Central
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Metanfetamina
Límite:
Animals
Idioma:
En
Revista:
Psychopharmacology (Berl)
Año:
2005
Tipo del documento:
Article
País de afiliación:
China