Effects of N-palmitoylethanolamide on anxiety-and depression-like behaviors in mice induced by chronic restraint stress / 中国病理生理杂志

ABSTRACT

AIM:To study the effects of N-palmitoylethanolamide ( PEA) on the anxiety-and depression-like behaviors of the mouse model induced by restraint stress , and to explore the possible mechanism of anxiolytic and antide-pressant effects of PEA .METHODS:The mice were intragastrically treated with 2.5, 5 and 10 mg/kg of PEA for 21 con-secutive days once daily .Thirty min after intragastric administration , the mice ( except the normal control group ) were placed in the glass tube to accept 4-h chronic restraint stress for 21 d.After the last administration , the mice were submit-ted to the forced stress test and the open field test (OFT) to observe the effects of PEA on the depression-like behaviors. The cumulative immobility time was recorded during the 4-min interval in the forced swimming test ( FST) or during the 5-min interval in the tail suspension test (TST).The elevated plus maze (EPM) test was used to investigate the effect of PEA on the mouse anxiety-like behaviors , and the water maze method was used to investigate the learning and memory abi-lities, spatial orientation and cognitive function of mice .After the behavior tests , the serum was collected and the hippo-campus was removed . The serum contents of adrenocorticotropic hormone ( ACTH ) , cortisol ( CORT ) and 5-hydroxytryptamine (5-HT) in the hippocampus were detected by ELISA .The changes of acetylcholinesterase ( AChE) ac-tivity in the hippocampal homogenate was measured by spectrophotometry .RESULTS:Compared with model group , in the FST or TST, the immobility time in the mice treated with PEA at 2.5~10 mg/kg and fluoxetine was significantly reduced . In the OFT, the total locomotion distance and total movement time were increased significantly in the mice , but only 10 mg/kg PEA and fluoxetine increased the numbers of rearing .In the EPM test , the percentage of the time spent in open arms, the entries into open arms and the total locomotion distance in 4 arms in the mice were significantly increased .In wa-ter maze test , PEA at 5 and 10 mg/kg and fluoxetine significantly shortened the latency to find the security zone in the mice, and PEA at 10 mg/kg and fluoxetine obviously shorten the swimming distance .Compared with model group , PEA at 10 mg/kg and fluoxetine reduced the mouse serum levels of ACTH and CORT , and the adrenal index , increased the 5-HT content and decreased the AChE activity in the hippocampus .CONCLUSION:PEA produces antagonistic effects on an-xiety-and depression-like behaviors in the mice induced by restraint stress .Its specific mechanism may be related to the re-gulation of the hypothalamic-pituitary-adrenal axis function by increasing the 5-HT level in hippocampus , thus participating in the regulation of central cholinergic system .