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. 2022 Mar 2;12(3):342.
doi: 10.3390/brainsci12030342.

Smo-Shh Agonist Purmorphamine Prevents Neurobehavioral and Neurochemical Defects in 8-OH-DPAT-Induced Experimental Model of Obsessive-Compulsive Disorder

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Smo-Shh Agonist Purmorphamine Prevents Neurobehavioral and Neurochemical Defects in 8-OH-DPAT-Induced Experimental Model of Obsessive-Compulsive Disorder

Ria Gupta et al. Brain Sci. .

Abstract

Obsessive-compulsive disorder is a mental disorder characterized by repetitive, unwanted thoughts and behavior due to abnormal neuronal corticostriatal-thalamocortical pathway and other neurochemical changes. Purmorphamine is a smoothened-sonic-hedgehog agonist that has a protective effect against many neurological diseases due to its role in maintaining functional connectivity during CNS development and its anti-inflammatory and antioxidant properties. As part of our current research, we investigated the neuroprotective effects of PUR against behavioral and neurochemical changes in 8-hydroxy-2-(di-n-propylamino)-tetralin-induced obsessive-compulsive disorder in rats. Additionally, the effect of PUR was compared with the standard drug for OCD, i.e., fluvoxamine. The intra-dorsal raphe-nucleus injection of 8-OH-DPAT in rats for seven days significantly showed OCD-like repetitive and compulsive behavior along with increased oxidative stress, inflammation, apoptosis, as well as neurotransmitter imbalance. These alterations were dose-dependently attenuated by long-term purmorphamine treatment at 5 mg/kg and 10 mg/kg i.p. In this study, we assessed the level of various neurochemical parameters in different biological samples, including brain homogenate, blood plasma, and CSF, to check the drug's effect centrally and peripherally. These effects were comparable to the standard oral treatment withfluvoxamine at 10 mg/kg. However, when fluvoxamine was given in combination with purmorphamine, there was a more significant restoration of these alterations than the individualtreatmentswithfluvoxamine and purmorphamine. All the above findings demonstrate that the neuroprotective effect of purmorphamine in OCD can be strong evidence for developing a new therapeutic target for treating and managing OCD.

Keywords: 8-OH-DPAT; Smo-Shh; fluvoxamine; obsessive-compulsive disorder; purmorphamine; serotonin.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Experiment protocol schedule.
Figure 2
Figure 2
Effect of purmorphamine on body weight in 8-OH OCD. Statistical analysis followed by two-way ANOVA (post-hoc Bonferroni’s test). Values expressed as mean ± SEM (n = 6 rats per group). * p < 0.01 v/s vehicle control, sham control and PUR10 per se; # p < 0.01 v/s 8-OH-DPAT; #$ p < 0.01 v/s 8-OH-DPAT + PUR5; #β p < 0.01 v/s 8-OH-DPAT + PUR5 and 8-OH-DPAT + PUR10; #@ p < 0.01 v/s 8-OH-DPAT + FLX10.
Figure 3
Figure 3
(a) Effect of purmorphamine on frequency of checking in 8-OH OCD. Statistical analysis followed by two-way ANOVA (post-hoc Bonferroni’s test). Values expressed as mean ± SEM (n = 6 rats per group). (b) Effect of purmorphamine on length of check in 8-OH OCD. Statistical analysis followed by two-way ANOVA (post-hoc Bonferroni’s test). (c) Effect of purmorphamine on recurrence time of checking in 8-OH OCD. Statistical analysis followed by two-way ANOVA (post-hoc Bonferroni’s test). (d) Effect of purmorphamine on number of stops before returning to key locale in 8-OH OCD. Statistical analysis followed by two-way ANOVA (post-hoc Bonferroni’s test). * p < 0.01 v/s vehicle control, sham control and PUR10 per se; # p < 0.01 v/s 8-OH-DPAT; #$ p < 0.01 v/s 8-OH-DPAT + PUR5; #β p < 0.01 v/s 8-OH-DPAT + PUR5 and 8-OH-DPAT + PUR10; #@ p < 0.01 v/s 8-OH-DPAT + FLX10.
Figure 4
Figure 4
Effect of purmorphamine on immobility time in 8-OH OCD. Statistical analysis followed by two-way ANOVA (post-hoc Bonferroni’s test). Values expressed as mean ± SEM (n = 6 rats per group). * p < 0.01 v/s vehicle control, sham control and PUR10 per se; # p < 0.01 v/s 8-OH-DPAT; #$ p < 0.01 v/s 8-OH-DPAT + PUR5; #β p < 0.01 v/s 8-OH-DPAT + PUR5 and 8-OH-DPAT + PUR10; #@ p < 0.01 v/s 8-OH-DPAT + FLX10.
Figure 5
Figure 5
Effect of purmorphamine on marble-burying behavior in 8-OH OCD. Statistical analysis followed by two-way ANOVA (post-hoc Bonferroni’s test). Values expressed as mean ± SEM (n = 6 rats per group). * p < 0.01 v/s vehicle control, sham control and PUR10 per se; # p < 0.01 v/s 8-OH-DPAT; #$ p < 0.01 v/s 8-OH-DPAT + PUR5; #β p < 0.01 v/s 8-OH-DPAT + PUR5 and 8-OH-DPAT + PUR10; #@ p < 0.01 v/s 8-OH-DPAT + FLX10.
Figure 6
Figure 6
Effect of purmorphamine on spontaneous alternation behavior in 8-OH OCD. Statistical analysis followed by two-way ANOVA (post-hoc Bonferroni’s test). Values expressed as mean ± SEM (n = 6 rats per group). * p < 0.01 v/s vehicle control, sham control and PUR10 per se; # p < 0.01 v/s 8-OH-DPAT; #$ p < 0.01 v/s 8-OH-DPAT + PUR5; #β p < 0.01 v/s 8-OH-DPAT + PUR5 and 8-OH-DPAT + PUR10; #@ p < 0.01 v/s 8-OH-DPAT + FLX10.
Figure 7
Figure 7
Effect of purmorphamine on excessive-lever-pressing behavior in 8-OH OCD. Statistical analysis followed by two-way ANOVA (post-hoc Bonferroni’s test). Values expressed as mean ± SEM (n = 6 rats per group). * p < 0.01 v/s vehicle control, sham control and PUR10 per se; # p < 0.01 v/s 8-OH-DPAT; #$ p < 0.01 v/s 8-OH-DPAT + PUR5; #β p < 0.01 v/s 8-OH-DPAT + PUR5 and 8-OH-DPAT + PUR10; #@ p < 0.01 v/s 8-OH-DPAT + FLX10.

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References

    1. Stein D.J., Costa D.L., Lochner C., Miguel E.C., Reddy Y.J., Shavitt R.G., van den Heuvel O.A., Simpson H.B. Obsessive–compulsive disorder. Nat. Rev. Dis. Primers. 2019;5:52. doi: 10.1038/s41572-019-0102-3. - DOI - PMC - PubMed
    1. Ruscio A.M., Stein D.J., Chiu W.T., Kessler R.C. The epidemiology of obsessive-compulsive disorder in the National Comorbidity Survey Replication. Mol. Psychiatry. 2010;15:53–63. doi: 10.1038/mp.2008.94. - DOI - PMC - PubMed
    1. Hazari N., Narayanaswamy J.C., Venkatasubramanian G. Neuroimaging findings in obsessive–compulsive disorder: A narrative review to elucidate neurobiological underpinnings. Indian J. Psychiatry. 2019;61((Suppl. 1)):S9. - PMC - PubMed
    1. Viol K., Schiepek G., Kronbichler M., Hartl A., Grafetstätter C., Strasser P., Kastinger A., Schöller H., Reiter E.M., Said-Yürekli S., et al. Multi-level assessment of obsessive-compulsive disorder (OCD) reveals relations between neural and neurochemical levels. BMC Psychiatry. 2020;20:559. doi: 10.1186/s12888-020-02913-5. - DOI - PMC - PubMed
    1. Westenberg H.G.M., Fineberg N.A., Denys D. Neurobiology of Obsessive-Compulsive Disorder: Serotonin and Beyond. CNS Spectrums. 2007;12:14–27. doi: 10.1017/S1092852900002479. - DOI