Modulation of extracellular signal-regulated kinases cascade by chronic delta 9-tetrahydrocannabinol treatment.
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.
Rubino
Tiziana
T
DBSF, Pharmacology Unit and Center of Neuroscience, University of Insubria, 21052 Busto Arsizio (VA), Italy.
Forlani
Greta
G
Viganò
Daniela
D
Zippel
Renata
R
Parolaro
Daniela
D
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
D020666:ras-GRF1; D013759:Dronabinol; D020928:Mitogen-Activated Protein Kinases