Effect of psilocybin on marble burying in ICR mice: role of 5-HT1A receptors and implications for the treatment of obsessive-compulsive disorder
Effect of psilocybin on marble burying in ICR mice: role of 5-HT1A receptors and implications for the treatment of obsessive-compulsive disorder
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Abstract Preliminary clinical findings, supported by preclinical studies employing behavioral paradigms such as marble burying, suggest that psilocybin may be effective in treating obsessive-compulsive disorder.However, the receptor mechanisms implicated in the putative anti-obsessional effect are not clear.On this background, we set out to explore (1) the role of serotonin 2A (5-HT2A) and serotonin 1A (5-HT1A) receptors in the effect of psilocybin on marble burying; (2) the effect of staggered versus bolus psilocybin administration and persistence of the effect; (3) the effect of the 5-HT1A partial agonist, buspirone, on marble-burying ut solution gel for cats and the head twitch response (HTR) induced by psilocybin, a rodent correlate of copyright effects.Male ICR mice were administered psilocybin 4.
4 mg/kg, escitalopram 5 mg/kg, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) 2 mg/kg, M100907 2 mg/kg, buspirone 5 mg/kg, WAY100635 2 mg/kg or combinations, intraperitoneally, and were tested on the marble burying test.HTR was examined in a magnetometer-based assay.The results show that (1) Psilocybin and escitalopram significantly reduced marble burying.The effect of psilocybin was not attenuated by the 5-HT2A antagonist, M100907.
The 5-HT1A agonist, 8-OH-DPAT, reduced marble burying as did the 5-HT1A partial agonist, buspirone.The effect of 8-OH-DPAT was additive to that of psilocybin, but that of buspirone was not.The 5-HT1A antagonist, WAY100635, attenuated the effect of 8-OH-DPAT and buspirone but not the effect of psilocybin.(2) Psilocybin injections over 3.
5 h had no effect on marble burying and the effect of bolus injection was not persistent.(3) Co-administration of buspirone with psilocybin blocked its effect on HTR.These data suggest that neither 5-HT2A nor 5-HT1A receptors are pivotally implicated in the effect of psilocybin on marble burying.Co-administration with buspirone may block the copyright effects of psilocybin without read more impeding its anti-obsessional effects.