Hyperactivity induced by the dopamine D-2/D-3 receptor agonist quinpirole is attenuated by inhibitors of endocannabinoid degradation in mice
Luque-Rojas, María Jesús
Santín Núñez, Luis Javier
Rodríguez de Fonseca, Fernando
MetadataShow full item record
The present study was designed to investigate the effect of pharmacological inhibition of endocannabinoid degradation on behavioural actions of the dopamine D-2/D-3 receptor agonist quinpirole in male C57Bl/6J mice. In addition, we studied the effects of endocannabinoid degradation inhibition on both cocaine-induced psychomotor activation and behavioural sensitization. We analysed the effects of inhibition of the two main endocannabinoid degradation enzymes : fatty acid amide hydrolase (FAAH), using inhibitor URB597 (1 mg/kg); monoacylglycerol lipase (MAGL), using inhibitor URB602 (10 mg/kg). Administration of quinpirole (1 mg/kg) caused a temporal biphasic response characterized by a first phase of immobility (0-50 min), followed by enhanced locomotion (next 70 min) that was associated with the introduction of stereotyped behaviours (stereotyped jumping and rearing). Pretreatment with both endocannabinoid degradation inhibitors did not affect the hypoactivity actions of quinpirole. However, this pretreatment resulted in a marked decrease in quinpirole-induced locomotion and stereotyped behaviours. Administration of FAAH or MAGL inhibitors did not attenuate the acute effects of cocaine. Furthermore, these inhibitors did not impair the acquisition of cocaine-induced behavioural sensitization or the expression of cocaine-induced conditioned locomotion. Only MAGL inhibition attenuated the expression of an already acquired cocaine-induced behavioural sensitization. These results suggest that pharmacological inhibition of endocannabinoid degradation might exert a negative feedback on D-2/D-3 receptor-mediated hyperactivity. This finding might be relevant for therapeutic approaches for either psychomotor disorders (dyskinesia, corea) or disorganized behaviours associated with dopamine-mediated hyperactivity.
Is part ofInternational Journal of Neuropsychopharmacology, 2013, vol. 16, núm. 3, p. 661-676
European research projects
Except where otherwise noted, this item's license is described as (c) CINP (Collegium Internationale Neuro-Psychopharmacologicum) , 2013
Showing items related by title, author, creator and subject.
Moderate and severe perinatal asphyxia induces differential effects on cocaine sensitization in adult rats Galeano, Pablo; Romero, Juan Ignacio; Luque-Rojas, María Jesús; Suárez, Juan; Holubiec, Mariana Inés; Bisagno, Verónica; Santín Núñez, Luis Javier; Rodríguez de Fonseca, Fernando; Capani, Francisco; Blanco Calvo, Eduardo (Wiley Periodicals, 2013-09-00)Perinatal asphyxia (PA) increases the likelihood of suffering from dopamine-related disorders, such as ADHD and schizophrenia. Since dopaminergic transmission plays a major role in cocaine sensitization, the purpose of ...
Oleoylethanolamide dose-dependently attenuates cocaine-induced behaviours through a PPARa receptor-independent mechanism Bilbao, Ainhoa; Blanco Calvo, Eduardo; Luque-Rojas, María Jesús; Suárez, Juan; Palomino, Ana; Vida, Margarita; Araos, Pedro; Bermúdez-Silva, Francisco J.; Fernández Espejo, Emilio; Spanagel, Rainer; Rodríguez de Fonseca, Fernando (John Wiley & Sons, 2013-01-00)Oleoylethanolamide (OEA) is an acylethanolamide that acts as an agonist of nuclear peroxisome proliferator-activated receptor alpha (PPARa) to exert their biological functions, which include the regulation of appetite and ...
Palmitoylethanolamide attenuates cocaine-induced behavioral sensitization and conditioned place preference in mice Zambrana Infantes, Emma; Rosell del Valle, Cristina; Ladrón de Guevara-Miranda, David; Galeano, Pablo; Castilla Ortega, Estela; Rodríguez de Fonseca, Fernando; Blanco Calvo, Eduardo; Santín Núñez, Luis Javier (Elsevier, 2018-01-08)Cocaine addiction is a chronically relapsing disorder characterized by compulsive drug-seeking and drug-taking behaviors. Previous studies have demonstrated that cocaine, as well as other drugs of abuse, alters the levels ...