RT Journal Article
T1 Pharmacological blockade of either cannabinoid CB1 or CB2 receptors prevents both cocaine-induced conditioned locomotion and cocaine-induced reduction of cell proliferation in the hippocampus of adult male rat.
A1 Blanco-Calvo, Eduardo
A1 Rivera, Patricia
A1 Arrabal, Sergio
A1 Vargas, Antonio
A1 Pavón, Francisco Javier
A1 Serrano, Antonia
A1 Castilla-Ortega, Estela
A1 Galeano, Pablo
A1 Rubio, Leticia
A1 Suárez, Juan
A1 Rodriguez de Fonseca, Fernando
K1 Cocaine
K1 Neurogenesis
K1 Cannabinoid receptors
K1 Rimonabant
K1 AM630
K1 Inflammation
K1 Hippocampus
K1 Striatum
K1 Cocaina
K1 Receptor cannabinoide CB1
K1 Receptor cannabinoide CB2
K1 Hipocampo
K1 Neostriado
K1 Ratas
AB Addiction to major drugs of abuse, such as cocaine, has recently been linked to alterations in adult neurogenesis in the hippocampus. The endogenous cannabinoid system modulates this proliferative response as demonstrated by the finding that pharmacological activation/blockade of cannabinoid CB1 and CB2 receptors not only modulates neurogenesis but also modulates cell death in the brain. In the present study, we evaluated whether the endogenous cannabinoid system affects cocaine-induced alterations in cell proliferation. To this end, we examined whether pharmacological blockade of either CB1 (Rimonabant, 3 mg/kg) or CB2 receptors (AM630, 3 mg/kg) would affect cell proliferation [the cells were labeled with 5-bromo-2'-deoxyuridine (BrdU)] in the subventricular zone (SVZ) of the lateral ventricle and the dentate subgranular zone (SGZ). Additionally, we measured cell apoptosis (as monitored by the expression of cleaved caspase-3) and glial activation [by analyzing the expression of glial fibrillary acidic protein (GFAP) and Iba-1] in the striatum and hippocampus during acute and repeated (4 days) cocaine administration (20 mg/kg). The results showed that acute cocaine exposure decreased the number of BrdU-immunoreactive (ir) cells in the SVZ and SGZ. In contrast, repeated cocaine exposure reduced the number of BrdU-ir cells only in the SVZ. Both acute and repeated cocaine exposure increased the number of cleaved caspase-3-, GFAP- and Iba1-ir cells in the hippocampus, and this effect was counteracted by AM630 or Rimonabant, which increased the number of BrdU-, GFAP-, and Iba1-ir cells in the hippocampus. These results indicate that the changes in neurogenic, apoptotic and gliotic processes that were produced by repeated cocaine administration were normalized by pharmacological blockade of CB1 and CB2. The restorative effects of cannabinoid receptor blockade on hippocampal cell proliferation were associated with the prevention of the induction of conditioned locomotion but not with the prevention of cocaine-induced sensitization.
PB Frontiers
YR 2014
FD 2014-01-08
LK http://hdl.handle.net/10668/1613
UL http://hdl.handle.net/10668/1613
LA en
NO Blanco-Calvo E, Rivera P, Arrabal S, Vargas A, Pavón FJ, Serrano A, et al. Pharmacological blockade of either cannabinoid CB1 or CB2 receptors prevents both cocaine-induced conditioned locomotion and cocaine-induced reduction of cell proliferation in the hippocampus of adult male rat. Front Integr Neurosci. 2014; 7:106
NO Journal Article;
DS RISalud
RD Mar 12, 2025