Study of neurogenic effects in cocaine-treated rats after CB1 and CB2 cannabinoid receptors blockade

BLANCO CALVO, EDUARDO; RIVERA-GONZÁLEZ, PATRICIA; ARRAVAL-NÚÑEZ, S; VARGAS, A; GALEANO, PABLO; SUÁREZ-PÉREZ, JUAN; CAPANI, FRANCISCO; SANTÍN NUÑEZ, LUIS JAVIER; RODRÍGUEZ DE FONSECA, FERNANDO

Munich

Congreso; 45th meeting of the European Brain and Behaviour Society; 2013

European Brain and Behaviour Society (EBBS)

Endocannabinoid system plays an essential role in the modulation of neurogenesis, neuroinflammation and cell death by modifying the activity of CB1 and CB2 receptors. Previously, we described the presence of several cannabinoids enzymes (DAGL, NAPE-PLD, FAAH, MAGL) in neurogenic brain regions. However, how these cellular processes are involved in drug addiction is still unknown. Therefore, we evaluated how the pharmacological blockade of CB1 and CB2 affects cell proliferation, astrogliosis and apoptosis during acute or sub-chronic cocaine administration. To this end, we measured the number of BrdU+ cells in subventricular zone (SVZ), dentate subgranular zone (SGZ) and ependymal-parenchymal area of the hypothalamus, and the number of caspase 3+, GFAP+ and Iba1+ cells in dorsal striatum, hippocampus and hypothalamus with rats, following either acute or repeated administration (5 days) of cocaine (20 mg/kg), or co-administration of cocaine with Rimonabant (3 mg/kg) or AM630 (3 mg/kg). Results showed that acute cocaine administration decreased the number of BrdU+ cells and increased the number of caspase 3+, GFAP+ and Iba1+ cells in the analyzed brain regions. Cocaine repeated administration reduced the number of BrdU+ cells in SVZ, the number of caspase 3+ cells in hippocampus, and Iba1+ and GFAP+ cells in hippocampus and hypothalamus. Repeated co-administration of cocaine with Rimonabant or AM630 increased the number of BrdU+ cells in all neurogenic regions, and decreased the number of caspase 3+ cells in hippocampus, GFAP+ cells in hippocampus and hypothalamus, and Iba1+ cells in striatum. These results indicate that neurogenic processes that are altered during sub-chronic cocaine administration were diminished by pharmacological modulation of CB1-2. In addition, this modulation decreased neuroinflammation and cell death. This study stimulates to further research if the pharmacological blockade of CB1-2 receptors could be a possible therapeutic strategy in the treatment of psychostimulant addiction.