the neuroprotective effect of lithium in cannabinoid dependence is mediated through modulation of cyclic amp, erk1/2 and gsk-3β phosphorylation in cerebellar granular neurons of rat

نویسندگان

seyed nasser ostad department of toxicology and pharmacology, faculty of pharmacy and pharmaceutical sciences research center, tehran university of medical sciences, tehran, iran

hamid reza rahimi department of toxicology and pharmacology, faculty of pharmacy and pharmaceutical sciences research center, tehran university of medical sciences, tehran, iran

mohammad hossein ghahremani department of toxicology and pharmacology, faculty of pharmacy and pharmaceutical sciences research center, tehran university of medical sciences, tehran, iran

ahmad reza dehpour department of pharmacology, faculty of medicine, tehran university of medical sciences, tehran, iran

چکیده

lithium (li), a glycogen synthase kinase-3β (gsk-3β) inhibitor, has used to attenuate thecannabinoid-induced dependence/withdrawal signs, but molecular mechanisms related to this areunclear. recent studies indicate the involvement of upstream extracellular signal kinase1/2 (erk1/2)and downstream gsk-3β pathways in the development of cannabinoid-induced dependence. thisis mediated through cannabinoid receptor 1 (cb1) enriched in cerebellar granular neurons (cgns).accordingly, the present study aimed to investigate the mechanism of modulatory/neuroprotectiveeffects of li on a cannabinoid agonist (win 55,212-2 (win))-induced dependence, throughquantitative analysis of some involved proteins such as erk1/2, gsk-3β and related signalingpathways including their phosphorylated forms; and camp level as the other molecular mechanismsleading to dependence, in cgns model. the cgns were prepared from 7-day-old wistar rat pup in a12-well plate, pretreated with li (1mm) and an erk1/2 inhibitor sl327 (sl, 10 μm). the win (1μm) was added 30 minutes prior to treatment and am251 (am, 1 μm), as a cannabinoid antagonistwas co-treated with win. the camp level, as an indicator of cannabinoid-induced dependence, wasmeasured by elisa following forskolin (fsk) stimulation. western blot analyses determined thephosphorylated forms of erk1/2 (p-erk1/2), gsk-3β (p-gsk-3β) as well as their total expressionsin various treatment times and doses in cgns. win alone could down regulate the camp/p-erk1/2cascade compared to am treatment. however, p-gsk-3β was up-regulated with li and win orwith sl and li pretreatment to am-induced cellular response, which was the highest 60 minutesafter cgns exposure. results further suggested the potential role of li pretreatment to diminishthe development of cannabinoid-induced dependence/neuronal injury through possible mechanismsof modulating the camp/p-erk1/2 cascade independent of p-gsk-3β signaling pathway in-vitro.

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The neuroprotective effect of lithium in cannabinoid dependence is mediated through modulation of cyclic AMP, ERK1/2 and GSK-3β phosphorylation in cerebellar granular neurons of rat

Lithium (Li), a glycogen synthase kinase-3β (GSK-3β) inhibitor, has used to attenuate thecannabinoid-induced dependence/withdrawal signs, but molecular mechanisms related to this areunclear. Recent studies indicate the involvement of upstream extracellular signal kinase1/2 (ERK1/2)and downstream GSK-3β pathways in the development of cannabinoid-induced dependence. Thisis mediated through cannab...

متن کامل

The neuroprotective effect of lithium in cannabinoid dependence is mediated through modulation of cyclic AMP, ERK1/2 and GSK-3β phosphorylation in cerebellar granular neurons of rat

Lithium (Li), a glycogen synthase kinase-3β (GSK-3β) inhibitor, has used to attenuate thecannabinoid-induced dependence/withdrawal signs, but molecular mechanisms related to this areunclear. Recent studies indicate the involvement of upstream extracellular signal kinase1/2 (ERK1/2)and downstream GSK-3β pathways in the development of cannabinoid-induced dependence. Thisis mediated through cannab...

متن کامل

The Neuroprotective Effect of Lithium in cannabinoid Dependence is Mediated through Modulation of Cyclic AMP, ERK1/2 and GSK-3β Phosphorylation in Cerebellar Granular Neurons of Rat

Lithium (Li), a glycogen synthase kinase-3β (GSK-3β) inhibitor, has used to attenuate the cannabinoid-induced dependence/withdrawal signs, but molecular mechanisms related to this are unclear. Recent studies indicate the involvement of upstream extracellular signal kinase1/2 (ERK1/2) and downstream GSK-3β pathways in the development of cannabinoid-induced dependence. This is mediated through ca...

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عنوان ژورنال:
iranian journal of pharmaceutical research

جلد ۱۴، شماره ۴، صفحات ۱۱۲۳-۱۱۳۵

کلمات کلیدی
[ ' d e p e n d e n c e ' , ' w i n 5 5 ' , 2 1 2 , 2 , ' c e r e b e l l a r g r a n u l a r n e u r o n s ' , ' i n ' , ' v i t r o ' , ' c y c l i c a m p ' ]

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