Effects of GPR55 Receptor Blockade on Schedule-Induced Polydipsia in Rats
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Authors
Lo, Lindsay
Date
Type
thesis
Language
eng
Keyword
GPR55 , Endocannabinoids , Compulsions , CB1 , Polydipsia
Alternative Title
Abstract
Compulsivity, a tendency toward repetitive, habitual actions that are repeated despite adverse consequences, is a core trait of many psychiatric pathologies. Despite its prevalence and severity, there are few effective pharmacological interventions for compulsive symptoms. The schedule-induced polydipsia (SIP) rodent model, in which chronically food-restricted animals develop adjunct compulsive drinking behaviours, has been used to investigate neurochemical substrates of compulsion. Recently, drinking behaviour was associated with bi-directional gamma-aminobutyric acid (GABA) plasticity signalling between G-protein-coupled receptor 55 (GPR55) mediated GABA potentiation and cannabinoid type I receptor (CB1) mediated GABA depression, in the bed nucleus of the stria terminalis (BNST). Compulsive, high drinking was correlated with deficient GPR55 GABA signalling. This project investigated a potential causal link between deficient GPR55 signaling and the development of compulsive drinking. We hypothesized that antagonism of GPR55, using CID 16020046 (CID), would turn low-drinking rats into high drinkers. However, administration of CID did not significantly increase water intake in low-drinking rats. Further, there was no difference in CID-induced water intake between animals displaying low vs high drinking behaviour. Animals receiving the higher CID dose elicited a greater increase in CID-induced water intake, although marginal, compared to the lower dose, irrespective of drinking classification. This suggests dosing may have been too low for a sufficient amount of CID to reach its target in the brain. In addition, the targeting of one receptor may not have been sufficient to evoke detectable behavioural changes, as a wide range of receptors and signalling systems have been implicated in the development of compulsive phenotypes. Regardless, this project served as a useful starting point to investigate a causal link between GPR55/CB1 signalling and the development of compulsive behaviour.
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CC0 1.0 Universal
ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.
CC0 1.0 Universal