RT Journal Article
T1 Effects of acute versus repeated cocaine exposure on the expression of endocannabinoid signaling-related proteins in the mouse cerebellum.
A1 Palomino, Ana
A1 Pavón, Francisco-Javier
A1 Blanco-Calvo, Eduardo
A1 Serrano, Antonia
A1 Arrabal, Sergio
A1 Rivera, Patricia
A1 Alén, Francisco
A1 Vargas, Antonio
A1 Bilbao, Ainhoa
A1 Rubio, Leticia
A1 Rodríguez de Fonseca, Fernando
A1 Suárez, Juan
K1 Cocaine
K1 Sensitization
K1 Cannabinoid
K1 Glutamate
K1 Tyrosine hidroxylase
K1 Mouse
K1 Cerebellum
K1 Cocaina
K1 Sensibilización del sistema nervioso central
K1 Cannabinoides
K1 Glutamatos
K1 Tirosina
K1 Ratones
K1 Cerebelo
AB Growing awareness of cerebellar involvement in addiction is based on the cerebellum's intermediary position between motor and reward, potentially acting as an interface between motivational and cognitive functions. Here, we examined the impact of acute and repeated cocaine exposure on the two main signaling systems in the mouse cerebellum: the endocannabinoid (eCB) and glutamate systems. To this end, we investigated whether eCB signaling-related gene and protein expression {cannabinoid receptor type 1 receptors and enzymes that produce [diacylglycerol lipase alpha/beta (DAGLα/β) and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD)] and degrade [monoacylglycerol lipase (MAGL) and fatty acid amino hydrolase (FAAH)] eCB} were altered. In addition, we analyzed the gene expression of relevant components of the glutamate signaling system [glutamate synthesizing enzymes liver-type glutaminase isoform (LGA) and kidney-type glutaminase isoform (KGA), metabotropic glutamatergic receptor (mGluR3/5), NMDA-ionotropic glutamatergic receptor (NR1/2A/2B/2C) and AMPA-ionotropic receptor subunits (GluR1/2/3/4)] and the gene expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, because noradrenergic terminals innervate the cerebellar cortex. Results indicated that acute cocaine exposure decreased DAGLα expression, suggesting a down-regulation of 2-arachidonylglycerol (2-AG) production, as well as gene expression of TH, KGA, mGluR3 and all ionotropic receptor subunits analyzed in the cerebellum. The acquisition of conditioned locomotion and sensitization after repeated cocaine exposure were associated with an increased NAPE-PLD/FAAH ratio, suggesting enhanced anandamide production, and a decreased DAGLβ/MAGL ratio, suggesting decreased 2-AG generation. Repeated cocaine also increased LGA gene expression but had no effect on glutamate receptors. These findings indicate that acute cocaine modulates the expression of the eCB and glutamate systems. Repeated cocaine results in normalization of glutamate receptor expression, although sustained changes in eCB is observed. We suggest that cocaine-induced alterations to cerebellar eCB should be considered when analyzing the adaptations imposed by psychostimulants that lead to addiction.
PB Frontiers
YR 2014
FD 2014-03-05
LK http://hdl.handle.net/10668/1608
UL http://hdl.handle.net/10668/1608
LA en
NO Palomino A, Pavón FJ, Blanco-Calvo E, Serrano A, Arrabal S, Rivera P, et al. Effects of acute versus repeated cocaine exposure on the expression of endocannabinoid signaling-related proteins in the mouse cerebellum. Front Integr Neurosci. 2014; 8:22
NO Journal Article;
DS RISalud
RD Apr 7, 2025