Investigation of Neurobiological Activity of a Neuropeptide (PYY3-36) in Mice

Mume, Celestine Okorome (2015-04-28)

Thesis

Peptide YY3-36 which is largely secreted by the L cells of the gastrointestinal tract, binds to the NPY Y2 receptor (Y2R) in the hypothalamus and inhibits food intake, however, there is no information on its neurobiological activity. Thus, the study investigated the effect of Peptide YY3-36 (PYY3-36) on locomotion, learning and memory, anxiety, depression and novelty-induced exploratory behaviour in both non-sleep deprived and sleep deprived mice. Saline or PYY3-36 (30 and 100 μg/kg) were administered intraperitonially (i.p.) to albino mice. Y-maze was used to determine the effect of PYY3-36 on locomotion, learning and memory. Both the holeboard and elevated plus maze models were used to measure exploratory and anxiolytic behaviours of PYY3-36. The mice were also subjected to forced swimming test to determine the possible antidepressant effect of the drug. Novelty-induced behaviours (rearing, grooming and burrowing) were assessed initially and then in a new set of mice following a 6 h total sleep deprivation. The role of cholinergic, opioid and GABA-benzodiazepine receptor systems in the effects of PYY3-36 was determined using scopolamine (cholinergic antagonist), naloxone (opioid antagonist) and flumazenil (GABA-benzodiazepine antagonist). The data were analysed statistically using analysis of variance (ANOVA) and post hoc Student Newman-Keuls test. The results showed that PYY3-36 significantly (p < 0.05) decreased rearing and increased grooming in non-sleep deprived mice but had no significant effect on burrowing. PYY3-36 demonstrated a significant (p < 0.05) reduction in anxiety level at a dose of 30 μg/kg. Scopolamine, naloxone and flumazenil reduced rearing while naloxone and flumazenil given with PYY3-36 further significantly decreased rearing. The administration of scopolamine 15 min before PYY3-36 administration did not reduce rearing compared to scopolamine alone. Scopolamine, naloxone and flumazenil significantly decreased grooming when given without PYY3-36. When these antagonists were administered 15 min prior to administration of PYY3-36, grooming remained significantly reduced. Scopolamine decreased burrowing while naloxone and flumazenil had no effect on burrowing but when given 15 min prior to the administration of PYY3-36 significantly decreased burrowing. Sleep deprivation reversed the decreased rearing and increased grooming induced by administration of PYY3-36. In conclusion, the study showed that PYY3-36 significantly reduced rearing and increased grooming behaviours respectively and revealed the involvement of opioid and GABA-benzodiazepine receptor systems in these effects. Futhermore, the study showed that Sleep deprivation modulated the activity of PYY3-36 on these behaviours.

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