title: Modulation of extracellular signal-regulated kinases cascade by chronic delta 9-tetrahydrocannabinol treatment.
abstract: Acute Delta(9)-tetrahydrocannabinol (THC) injection increased ERK pathway (ERK, pCREB, and c-fos) mostly in the caudate putamen and cerebellum. This effect underwent to homeostatic adaptation after chronic treatment. Moreover, chronic THC exposure induced increases in the ERK cascade (ERK, pCREB, and Fos B) in the prefrontal cortex and hippocampus, suggesting that different neuronal circuits seem to be involved in the early phase and late phase of exposure. The involvement of ERK pathway in cannabinoid chronic exposure was also confirmed in Ras-GRF1 knock out mice, a useful model where cannabinoid-induced ERK activation is lost. In fact, Ras-GRF1 ko mice did not develop tolerance to THC analgesic and hypolocomotor effect. Our data suggest that ERK cascade could play a pivotal role in the induction of synaptic plasticity due to cannabinoid chronic exposure.
authors.affiliation: DBSF, Pharmacology Unit and Center of Neuroscience, University of Insubria, 21052 Busto Arsizio (VA), Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Rubino
authors.forename: Greta
authors.initials: G
authors.lastname: Forlani
authors.forename: Daniela
authors.initials: D
authors.lastname: Viganò
authors.forename: Renata
authors.initials: R
authors.lastname: Zippel
authors.forename: Daniela
authors.initials: D
authors.lastname: Parolaro
mesh_terms: D000818:Animals; D013759:Dronabinol / Q000494:pharmacology*; D004334:Drug Administration Schedule; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020666:ras-GRF1 / Q000172:deficiency / Q000235:genetics
chemical_list: D020666:ras-GRF1; D013759:Dronabinol; D020928:Mitogen-Activated Protein Kinases