IBCN   20355
INSTITUTO DE BIOLOGIA CELULAR Y NEUROCIENCIA "PROFESOR EDUARDO DE ROBERTIS"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
RELATIONSHIP BETWEEN CEREBELLAR CORTEX EXPRESSION OF CB1-R, CB2-R, GABA AND GLAST-1 AFTER CHRONIC AGONIST CANNABINOID EXPOSURE IN ADULT MALE RAT
Autor/es:
CALTANA LR; TAGLIAFERRO P; SAEZ T; ONAIVI E; BRUSCO ALICIA
Lugar:
Buzios, Brasil
Reunión:
Congreso; Ier CongresoIBRO/LARC de Neurociencias de America Latina, Caribe y Península Ibérica. XXIII Congreso de la Sociedad Argentina de Investigación en Neurociencias; 2008
Resumen:
There are two well characterized cannabinoid receptors (CB-Rs) that mediate the effects of endocannabinoids and cannabis use. CB1-Rs are mainly presynaptic and are G-protein coupled, while CB2-Rs are mainly postsynaptic and both are present in cerebellar cortex. WIN 55,212-2 is an agonist that activates both types of CB-Rs. The Purkinje cell is the only projection neuron of cerebellar cortex and is a GABAergic neuron with a rich dendritic tree in the molecular layer. In order to study the response of the cerebellar cortex CB1-R and CB2-R to a cannabinoid agonist exposure we used an animal model of rats treated with WIN55,212-2. Ten adult male Wistar rats were divided into 2 groups: one group of 5 animals (treated group = W) were injected twice daily subcutaneously with WIN55212-2, mesylate (3mg/kg) dissolved in DMSO for 14 days. The other 5 rats (control group = C) were injected with an equivalent volume of sterile DMSO. On the fifteenth day, rats were perfused intracardiacally with 4% paraformaldehyde in 0.1M phosphate buffer. 50 µm thick sections were obtained using a vibratome. Sections were immunostained using primary antibody to CB1-R, CB2-R, GABA and GLAST-1 (a glial glutamate transporter). In the basket of Purkinje cells, there was decreased CB1-R immunoreactivity (ir), determined by measuring the relative area of ir (C: 2.8 ± 0.11 vs. W: 1.66 ± 0.10 [P=0.02]) and for GABA-ir (C: 0.15 ± 0.01 vs. W 0.06 ± 0.007 [P<0.0001]). In contrast the treatment with WIN55,212-2 increased the percentage of CB2-R-ir (C: 0.137 ± 0.02 vs. W: 0.38 ± 0.02 [P<0.0001]) and GLAST-1-ir (C: 0.10 ± 0.008 vs. W: 0.32 ± 0.01 [P<0.0001]) in the molecular layer. The present results showed that chronic treatment with cannabinoid agonist modified the expression CB-Rs, GABA, and GLAST-1 in the cerebellar cortex. We conclude, that chronic treatment with WIN55,212,2 produced dowregulation of CB1-R expression and reduced the expression of GABA in Purkinje´s basket cells. However, the increase in the expression of CB2-R may be associated with inflammatory response that may be related with an astrocytic reaction modulated by the increase in the GLAT-ir. Keywords: drug abuse, cannabinoid agonist