title: Cocaine facilitates protein synthesis-dependent LTP: the role of metabotropic glutamate receptors.
abstract: Cocaine addiction alters synaptic plasticity in many brain areas involved in learning and memory processes, including the hippocampus. Long-term potentiation (LTP) is one of the best studied examples of hippocampal synaptic plasticity and it is considered as one of the molecular basis of learning and memory. We previously demonstrated that in the presence of cocaine, a long lasting form of hippocampal LTP is induced by a single pulse of high frequency stimulation, which in normal conditions evokes only an early form of LTP. In this study, we further explore the molecular basis of this modulation of synaptic plasticity by cocaine. By performing pharmacological experiments on hippocampal slices, we were able to show that cocaine converts early LTP to a form of LTP dependent on protein synthesis, probably through the cAMP-dependent protein kinase and extracellular signal-regulated kinase signaling cascades. We also found that metabotropic glutamate receptors are involved in this phenomenon. These studies further clarify the molecular machinery used by cocaine to alter synaptic plasticity and modulate learning and memory processes.
authors.affiliation: Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad CEU-San Pablo, Madrid, Spain; Departamento de Psicobiología, Facultad de Psicología, UNED, 28040 Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Fole
authors.affiliation: Departamento de Psicología Básica I, Facultad de Psicología, UNED, 28040 Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Miguens
authors.affiliation: Departamento de Psicobiología, Facultad de Psicología, UNED, 28040 Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Higuera-Matas
authors.affiliation: Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad CEU-San Pablo, Madrid, Spain; Unidad de Investigación Traslacional, Hospital de Ciudad Real, Spain.
authors.forename: L F
authors.initials: LF
authors.lastname: Alguacil
authors.affiliation: Departamento de Psicobiología, Facultad de Psicología, UNED, 28040 Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Ambrosio
authors.affiliation: Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad CEU-San Pablo, Madrid, Spain. Electronic address: nolmo@ceu.es.
authors.forename: N
authors.initials: N
authors.lastname: Del Olmo
mesh_terms: D000818:Animals; D003042:Cocaine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011619:Psychotropic Drugs / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D009419:Nerve Tissue Proteins; D047428:Protein Kinase Inhibitors; D011500:Protein Synthesis Inhibitors; D011619:Psychotropic Drugs; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D017868:Cyclic AMP-Dependent Protein Kinases; D003042:Cocaine
keywords: Cocaine; Dopamine and PKA; ERK; Hippocampus; LTP; Learning; Metabotropic glutamate receptors; Plasticity