Regulation by phosphodiesterase of anxiety-and depressive-like behavior induced by alcohol withdrawal in mice

OBJECTIVE Alcohol dependence is not only the most common public health prob⁃lem worldwide,but also the cause of many alco⁃hol-related diseases,such as anxiety and depres⁃sion.However,the mechanism of these comor⁃bidities is not clear.Recently,the role of phos⁃phodiesterases(PDEs)in anxiety-and depres⁃sion-like behavior induced by alcohol withdrawal has received increasing attentions.PDEs are a superfamily of enzymes that catalyze the hydroly⁃sis of intracellular cyclic AMP(cAMP)and(or)cyclic GMP(cGMP).There are 11 families(PDE1-PDE11),each of which has 1 to 4 sub⁃types encoded by different genes.In the present study,we identified the key PDEs involved in anxiety-and depression-like behavior induced by alcohol withdrawal.METHODS After withdrawal from short-term or chronic intermittent ethanol vapor exposure(STEVE and CIEVE,respectively),adult male C57BL/6J(B6)mice were tested for anxiety-and depression-like behavior using the sucrose preference,open field,elevated plus-maze,tail suspension,forced swimming,hole board and light-dark tests.In addition,the expression of PDE subtypes(PDE2,PDE4,and PDE7)in the hippocampus,amygdala,and stria⁃tum,which are considered as anxiety-and(or)depression-related brain regions,was detected by Western blotting.RESULTS①Differences in anxiety-and depression-like behaviors between STEVE and CIEVE mice.Compared to STEVE mice,CIEVE mice showed greater anxiety-and depression-like behavior in the tests described above.②The expression of PDE2,PDE4 and PDE7 in the anxiety-and depression-related brain regions of CIEVE mice.Compared to the STEVE mice,CIEVE mice showed significant higher expression of PDE4A and PDE7A in the hippo⁃campus(P<0.05)and PDE4D and PDE7A in the amygdala(P<0.05).However,the expres⁃sion of PDE2A,PDE4B,PDE4D and PDE7B in the hippocampus,PDE2A,PDE4A,PDE4B and PDE7B in the amygdala,PDE2A,PDE4A,PDE4B,PDE4D,PDE7A and PDE7B in the striatum was not significantly changed.CONCLUSION The model of CIEVE showed significant anxiety-and depression-like behavior,with concurrent increases in the expression of PDE4A and PDE7A in the hippocampus and PDE4D and PDE7A in the amygdala.These results suggest that PDE4A,PDE4D,and DE7A may play an important role in the regulation of anxiety-and depression-like behavior induced by alcohol withdrawal.