Leptin and insulin signaling on midbrain dopamine neurons do not modulate anxiety and depression behaviours
Kumar, Nivesh
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Cite this item:
Kumar, N. (2018). Leptin and insulin signaling on midbrain dopamine neurons do not modulate anxiety and depression behaviours (Thesis, Master of Science). University of Otago. Retrieved from http://hdl.handle.net/10523/8232
Permanent link to OUR Archive version:
http://hdl.handle.net/10523/8232
Abstract:
Anxiety is a highly aroused negative emotional state that occurs in response to potential danger, and can be inappropriately intensified due to aberrations in the aversion pathway of mesocorticolimbic dopamine circuitry. Anxiety, and co- morbid depression that is also affected by the mesocorticolimbic dopamine circuitry, also interact with the metabolic system. The metabolic hormone leptin decreases mesocorticolimbic dopamine activity while insulin may have mixed effects on these neurons. Deletions of leptin receptors from dopamine neurons and insulin receptors from cells throughout the brain have been shown to produce anxiogenic behaviours. Therefore, the aims of this study are to assess anxiety- and depression-related behaviours due to leptin and insulin receptor deletions from dopamine neurons, and also to identify possible compensatory overlapping roles of leptin and insulin on DA neurons in the control of anxiety- and depression-related behaviours, by deleting both types of receptors simultaneously.The Cre/loxP system was employed to generate male and female C57BL/6J mice lacking either functional leptin or insulin receptors (single knockouts) or both receptors (double knockouts) on dopamine neurons (targeted using a DAT- Cre mouse line, in which the dopamine transporter gene promoter is modified to also produce the enzyme Cre recombinase). Receptor knockout and control (Cre non-expressing) littermates were assessed for anxiety-related behaviour via the elevated plus maze, open field test and light-dark box, and depression-related behaviour via the forced swim test and sucrose preference test.The single knockouts and double knockouts were not significantly different from controls in their performance in both anxiety (i.e. time spent in the open or lighted areas) and depression (duration of escape behaviour and hedonic preference for sucrose) tests. There was also no difference in basal plasma corticosterone concentration across the groups. It was concluded that direct leptin and insulin signaling on DA neurons do not affect anxiety- and depression-related behaviours. In comparison with a previously published DA neuron leptin receptor knockout study that showed an anxious phenotype, this study did not show anxiogenic results. However, the anxiogenic results from the previously published study may be explained by the more anxiogenic conditions that the experimental animals were exposed to. Furthermore, due to no phenotypical difference between single- and double-knockout animals, the role of leptin and insulin exerting compensatory overlapping roles on DA neurons with regard to anxiety- and depression-related behaviours is uncertain.
Date:
2018
Advisor:
Anderson, Greg Muir; Evans, Maggie
Degree Name:
Master of Science
Degree Discipline:
Anatomy
Publisher:
University of Otago
Keywords:
Anxiety; depression; dopamine; leptin; insulin; VTA
Research Type:
Thesis
Languages:
English
Collections
- Anatomy [249]
- Thesis - Masters [4213]