Lopez-Grancha M

References (3)

Title : Selective blockade of the hydrolysis of the endocannabinoid 2-arachidonoylglycerol impairs learning and memory performance while producing antinociceptive activity in rodents - Griebel_2015_Sci.Rep_5_7642
Author(s) : Griebel G , Pichat P , Beeske S , Leroy T , Redon N , Jacquet A , Francon D , Bert L , Even L , Lopez-Grancha M , Tolstykh T , Sun F , Yu Q , Brittain S , Arlt H , He T , Zhang B , Wiederschain D , Bertrand T , Houtmann J , Rak A , Vallee F , Michot N , Auge F , Menet V , Bergis OE , George P , Avenet P , Mikol V , Didier M , Escoubet J
Ref : Sci Rep , 5 :7642 , 2015
Abstract : Monoacylglycerol lipase (MAGL) represents a primary degradation enzyme of the endogenous cannabinoid (eCB), 2-arachidonoyglycerol (2-AG). This study reports a potent covalent MAGL inhibitor, SAR127303. The compound behaves as a selective and competitive inhibitor of mouse and human MAGL, which potently elevates hippocampal levels of 2-AG in mice. In vivo, SAR127303 produces antinociceptive effects in assays of inflammatory and visceral pain. In addition, the drug alters learning performance in several assays related to episodic, working and spatial memory. Moreover, long term potentiation (LTP) of CA1 synaptic transmission and acetylcholine release in the hippocampus, two hallmarks of memory function, are both decreased by SAR127303. Although inactive in acute seizure tests, repeated administration of SAR127303 delays the acquisition and decreases kindled seizures in mice, indicating that the drug slows down epileptogenesis, a finding deserving further investigation to evaluate the potential of MAGL inhibitors as antiepileptics. However, the observation that 2-AG hydrolysis blockade alters learning and memory performance, suggests that such drugs may have limited value as therapeutic agents.
ESTHER : Griebel_2015_Sci.Rep_5_7642
PubMedSearch : Griebel_2015_Sci.Rep_5_7642
PubMedID: 25560837
Gene_locus related to this paper: mouse-ABHD6

Title : Vulnerability of long-term neurotoxicity of chlorpyrifos: effect on schedule-induced polydipsia and a delay discounting task - Cardona_2006_Psychopharmacology.(Berl)_189_47
Author(s) : Cardona D , Lopez-Grancha M , Lopez-Crespo G , Nieto-Escamez F , Sanchez-Santed F , Flores P
Ref : Psychopharmacology (Berl) , 189 :47 , 2006
Abstract : INTRODUCTION: Chlorpyrifos (CPF) is a common organophosphate (OP) insecticide that has been widely used in extensive agriculture as a pesticide. The primary mechanism of acute toxic action of OPs is inhibition of acetylcholinesterase (AChE). However, targets other than AChE have been proposed to contribute to the acute lethal action and side effects of short- or long-term exposure to these compounds. Bekkedal et al. (Sci Total Environ 274:119-123;2001) showed that chronic administration of the OP trimethylolpropane phosphate (TMPP) reduces the number of schedule-induced polydipsia (SIP) sessions necessary to induce asymptotic drinking level. MATERIALS AND
METHODS: In the present work, rats were injected with 250 mg/kg CPF and 6 months later, its effect on schedule-induced polydipsia was evaluated. In addition, after stable levels of SIP, a pharmacological study was carried out to determine the implication of other systems in the long-term effects of OPs. Finally, these animals were evaluated in a delay discounting task, as a measure of impulsivity.
RESULTS: Results indicate that the CPF group gives more licks to obtain the same amount of water than control rats (VHC). Moreover, the administration of diazepam produces an increased water intake in the CPF without any observable effect in VHC rats. Data of the delay discounting task show that CPF rats prefer an immediate reward and show a major impulsive choice. DISCUSSION: Taken together, our data confirm and extend the long-term behavioral effects of subcutaneous administration of CPF and point to a role for other systems that, besides AChE inhibition, contribute to the long-term neurotoxicity of CPF.
ESTHER : Cardona_2006_Psychopharmacology.(Berl)_189_47
PubMedSearch : Cardona_2006_Psychopharmacology.(Berl)_189_47
PubMedID: 17016712

Title : Long-term functional neurotoxicity of paraoxon and chlorpyrifos: behavioural and pharmacological evidence - Sanchez-Santed_2004_Neurotoxicol.Teratol_26_305
Author(s) : Sanchez-Santed F , Canadas F , Flores P , Lopez-Grancha M , Cardona D
Ref : Neurotoxicology & Teratology , 26 :305 , 2004
Abstract : Organophosphate (OP) compounds are chemicals widely used in agriculture, industry and households and even as chemical weapons. The major mechanism of acute toxic action is the inhibition of acetylcholinesterase (AChE), which is responsible for the degradation of the neurotransmitter acetylcholine. A chronic OP-induced neuropsychiatric disorder (COPIND), which could result from both long-term exposure to subclinical doses of OP and after acute intoxication, has been proposed. These reports claim to develop animal models that could parallel behavioural and cognitive effects and that could later help to elucidate the mechanisms involved in this long-term affectation of the central nervous system. The present study uses a series of behavioural tests to discern the short- and long-term effects of acute intoxications with paraoxon (Px) or chlorpyrifos (CPF). Our results suggest that months after acute exposure to these OPs functional central nervous system alterations can be detected using a repeated acquisition spatial task in the water maze, for CPF, and in amphetamine-induced place preference paradigm, for both Px and CPF.
ESTHER : Sanchez-Santed_2004_Neurotoxicol.Teratol_26_305
PubMedSearch : Sanchez-Santed_2004_Neurotoxicol.Teratol_26_305
PubMedID: 15019964