Changes in the cannabinoid receptor binding, G protein coupling, and cyclic AMP cascade in the CNS of rats tolerant to and dependent on the syntheticcannabinoid compound CP55,940

Citation
T. Rubino et al., Changes in the cannabinoid receptor binding, G protein coupling, and cyclic AMP cascade in the CNS of rats tolerant to and dependent on the syntheticcannabinoid compound CP55,940, J NEUROCHEM, 75(5), 2000, pp. 2080-2086
Citations number
30
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROCHEMISTRY
ISSN journal
00223042 → ACNP
Volume
75
Issue
5
Year of publication
2000
Pages
2080 - 2086
Database
ISI
SICI code
0022-3042(200011)75:5<2080:CITCRB>2.0.ZU;2-X
Abstract
Chronic exposure to CP55,940 produced a significant down-regulation of cann abinoid receptors in the striatum, cortex, hippocampus, and cerebellum of r at brain. At 24 h after SR141716-precipitated withdrawal, we observed a ten dency to return to basal levels in the striatum and cortex, whereas the spe cific binding remained lower in the hippocampus and cerebellum. When we sur veyed cannabinoid receptor-activated G proteins, in chronic CP55,940-treate d rats the guanosine 5'-O-(3-[S-35]thiotriphosphate) ([S-35]GTP gamma S) bi nding assay revealed a decrease of activated G proteins in the striatum, co rtex, and hippocampus, whereas no significant changes were seen in the cere bellum. At 24 h after the SR141716-precipitated withdrawal, [S-35]GTP gamma S binding increased compared with that of rats chronically exposed to CP55 ,940, attaining the control level except for cerebellum, where we observed a trend to overcome the control amounts. Concerning the cyclic AMP (cAMP) c ascade, which represents the major intracellular signaling pathway activate d by cannabinoid receptors, in the cerebral areas from rats chronically exp osed to CP55,940 we found alteration in neither cAMP levels nor protein kin ase A activity. In the brain regions taken from CP55,940-withdrawn rats, we only observed a significant up-regulation in the cerebellum. Our findings suggest that receptor desensitization and down-regulation are strictly invo lved in the development of cannabinoid tolerance, whereas alterations in th e cAMP cascade in the cerebellum could be relevant in the mediation of the motor component of cannabinoid abstinence.