Thesis

Role of proteinase-activated receptor-2 in central mediated behaviour

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Awarding institution
  • University of Strathclyde
Date of award
  • 2014
Thesis identifier
  • T13684
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Abstract
  • Proteinase-activated receptors (PARs) are a family of novel G protein-coupled receptors, which are widely expressed in the brain. It has been recently shown that PAR2 activation indirectly modulates hippocampal neuronal excitability and synaptic transmission in vitro, and treatment with the PAR2 agonist SLIGRL-NH2 induced deficits in tests of motivational learning in rats. Hence, in this study we have investigated whether PAR2 deletion affects mouse behaviour in tests of learning and emotional behaviours under physiological and pathological conditions. Deletion of PAR2 had no effect on locomotor activity in the open field test. Heterozygous males appeared more anxious in the open field test but knockout females exhibited less anxiety in the elevated plus maze. PAR2 deletion had no effect on spatial reference memory in the Morris water maze but reduced mean percent alternation to chance level in the T-maze continuous alternation test and produced deficits in the male mice in the novel object recognition test. Deletion of PAR2 did not affect general startle reactivity and sensorimotor gating but it decreased the startle response at the highest stimuli in females. In a sickness behaviour model, deletion of PAR2 delayed induction of anhedonia as measured in the sucrose preference test after injection of lipopolysaccharide. It also induced a more rapid recovery from other symptoms of sickness behaviour as shown by increased locomotor activity 24 and 48 h post injection, increased body weight at 48 and 72 h post injection, increased food intake during the second day post injection and reduced anxiety-like behaviour 24 h post injection. The novel PAR2 agonist AC-264613 penetrated into mouse brain. AC-264613 had no effects on locomotor activity and anxiety-like behaviour but showed a tendency to induce anhedonia. In conclusion, these data indicate that proteinase-activated receptor-2 may be involved in mouse behaviour under normal and pathological conditions.
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DOI
Date Created
  • 2014
Former identifier
  • 1027211

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