ABSTRACT
Anorexia Nervosa (AN) is an eating and behavioral disorder characterized with anxiety/depression, hyperactivity, behavioral impulsivity and psychosis. Most of the associated symptoms are related to the deficiency of serotonin (5-hydroxytryptamine: 5-HT) stores. A deficiency of 5-HT can modulate dopamine neurotransmission in the striatum to elicit hyperactivity and psychosis in AN patients. Also, the release and availability of 5-HT are modulated by serotonin-1A (5-HT1A) auto-receptor. The present study investigates the role of striatal metabolism of 5-HT and dopamine in precipitating hyperactivity in the rat model of diet restriction (DR) induced AN. The role of tryptophan (Trp) in influencing the 5-HT metabolism and the mRNA expression of 5-HT1A auto-receptor is also investigated. We find that long-term DR for 38 days reduces body-weight in rats and produces hyperactivity, similar to AN. This hyperactivity is characterized by declined striatal metabolism of both, dopamine and 5-HT. The mRNA expression of 5-HT1A auto-receptor in the raphe nuclei is also decreased. Trp co-treatment improves these deficiencies in monoamine metabolism and alleviates hyperactivity. Interestingly, DR-induced changes in body-weights are not effected by Trp co-treatment. The study suggests that the striatal metabolism of 5-HT and dopamine and mRNA expression of 5-HT1A auto-receptor has an important role in the pathogenesis of AN. The finding suggests that co-use of Trp can prevent precipitation of AN by normalizing 5-HT metabolism.
Acknowledgements
The study was supported by Faculty grant from Dr Panjwani Center for Molecular Medicine and Drug Research, University of Karachi. Research grant from National Research Program for Universities, Higher Education Commission, Pakistan. Project no.: 7247/Sindh/NRPU/R&D/HEC/2017.
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No potential conflict of interest was reported by the author(s).
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Notes on contributors
Raheel Saeed
Raheel Saeed is a research associate, working under the supervision of Prof. Dr. Darakhshan Jabeen Haleem at Dr Panjwani Centre for Molecular Medicine and Drug Research, University of Karachi.
Khalid Mahmood
Khalid Mahmood is a research associate, working for the Ph.D. in the supervision of Prof Dr Darakhshan Jabeen Haleem at Dr Panjwani Centre for Molecular Medicine and Drug Research, University of Karachi.
Sadia Basharat Ali
Sadia Basharat Ali is a research associate, working for the M. Phil. in the supervision of Prof Dr Darakhshan Jabeen Haleem at Dr Panjwani Centre for Molecular Medicine and Drug Research, University of Karachi.
Darakhshan Jabeen Haleem
Darakhshan Jabeen Haleem is meritorious Professor of Neuroscience at Dr Panjwani Center for Molecular Medicine and Drug Research, University of Karachi. She did Ph.D. from the Institute of Neurology, London University in 1988 and is associated with the University of Karachi since 1980. She is author of many research and review articles published in high impact journals.