Feliszek, Monika Wanda: Age-dependent cannabinoid CB1 receptor plasticity and search for histamine H4 receptors in the brain. - Bonn, 2016. - Dissertation, Rheinische Friedrich-Wilhelms-Universität Bonn.
Online-Ausgabe in bonndoc: https://nbn-resolving.org/urn:nbn:de:hbz:5n-44911
urn: https://nbn-resolving.org/urn:nbn:de:hbz:5n-44911,
author = {{Monika Wanda Feliszek}},
title = {Age-dependent cannabinoid CB1 receptor plasticity and search for histamine H4 receptors in the brain},
school = {Rheinische Friedrich-Wilhelms-Universität Bonn},
year = 2016,
month = oct,

note = {The aim of this thesis was to examine whether adaptive changes of cannabinoid CB1 receptors occur following their direct and indirect activation through pre-treatment with an exogenous and endogenous cannabinoid depending on age and whether histamine H4 receptor mRNA and functional H4 receptors occur in the brain.
This thesis focuses on the 35S-GTPγS binding assay combined with other experimental methods. The motility of the mice after Δ9-THC treatment was studied in the Open Field Test. The concentration of the endogenous cannabinoid 2-arachidonoyl glycerol (2-AG) after JZL 184 treatment in the hippocampus was determined by liquid chromatography tandem mass spectrometry. Histamine H4 receptor in the hippocampus of the mouse and guinea pig was detected using the reverse transcriptase polymerase chain reaction.
Adolescent and aged mice were administered i.p. with Δ9-THC acute (single injection as a challenge dose) or chronically (6 injections over 3 days and a challenge dose), subsequently the motility of the animals was measured and CB1 receptor G-Protein activation was quantified using 35S-GTPγS binding method. A single dose of Δ9-THC decreased the motility in adolescent and old animals. Pre-treatment of mice with Δ9-THC attenuated the effect of a challenge dose of Δ9-THC by about 50 % in the rearing and resting time paradigm, independent of the age; with respect to the distance travelled, the attenuation of the effect tended to be less pronounced in old when compared to adolescent mice. Basal 35S-GTPγS binding was lower in hippocampal membranes from vehicle-treated aged when compared to adolescent mice whereas Δ9-THC pre-treatment decreased basal binding significantly in adolescent but had no effect in membranes from old mice. The increase in CP 55,940-induced 35S-GTPγS binding was less marked in vehicle-treated old than in adolescent mice. After pre-treatment with Δ9-THC, the CP 55,940-related increase in 35S-GTPγS binding was not affected in old but was significantly reduced in adolescent mice. The results show that aging affects basal and CP 55,940-induced 35S-GTPγS binding and the tolerance development of both parameters to Δ9-THC pre-treatment; in the behavioural paradigm, aging does not influence tolerance development.
In the second part the concentration of 2-AG was increased by blockade of its degrading enzyme by JZL 184 and the effect of 2-AG on basal and CP 55,940-induced 35S-GTPγS binding was measured. Adolescent mice were pre-treated with JZL 184 at 4, 10 or 40 mg/kg over a period of 14 days. JZL 184 at 4 mg/kg and 10 mg/kg did not affect measured parameters and increased hippocampal 2-AG without affecting CP 55,940-induced 35S-GTPγS binding, respectively. JZL 184 at 40 mg/kg increased 2-AG but also tended to decrease the CP 55,940-induced 35S-GTPγS binding. The data suggest that 10 mg/kg of JZL 184 when administered over a longer time period leads to a sustained increase in 2-AG and does not cancel out the activation of CB1 receptors.
In the third part the H4 receptor mRNA is was detected in the cerebral cortex of mice and guinea pigs. The search for a functional correlate was, however, negative; thus, a H4 receptor-related facilitation of 35S-GTPγS binding in cortical membranes of either species could not be shown.},

url = {http://hdl.handle.net/20.500.11811/6895}

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