Objective
Endogenous opioids and cannabinoids are profoundly active in regulating corresponding receptor systems that are almost ubiquitous in mammalian nervous system, both central and peripheral. They are involved in the functions as important as learning, memory, pain processing etc. Pharmacological use of opioids and cannabinoids lasts for millennia. Even in modern times the use of opioids remains ultima ratio in the treatment of severe pain. However, their use demands extreme caution and is subjected to severe limitations due to well known side effects such as drug abuse which is a global social threat. Impairments of learning and memory represent the most commonly reported behavioral effects of opiates and cannabinoids. Numerous data from different labs, including ours, indicate that these effects, when examined in vitro, have their correlate in synaptic plasticity. The general aim of this project is to test the hypothesis, that opiates and cannabinoids affect synaptic plasticity in hippocampus through modulating P2X receptors and P-type calcium channels. For this purpose we will pursue the following specific objectives: (i) Do opiates and cannabinoids modulate the P2X receptors and Ca channels? (ii) What are the molecular mechanisms of opiates/cannabinoids-dependent modulation of P2X receptors and Ca channels? (iii) How opiates/cannabinoids-dependent modulation of P2X receptors and Ca2+ channels affects the long-term synaptic plasticity? To answer these specific questions we will investigate hippocampal and cortical neurones by a combination of state-of-the art electrophysiological and real time [Ca2+]i imaging techniques. We shall characterise in detail the effects of opiates/cannabinoids on (i) P2X receptors and voltage-gated Ca2+ channels, (ii) neuronal Ca2+ signalling and on (iii) synaptic transmission and long-term plasticity. Further we shall identify molecular mechanisms by which opiates/cannabinoids affect P2X receptors and Ca2+ channels and reveal the pathways for opioid/cannabinoid receptors interactions with P2X receptors/Ca2+ channels in the animals subjected to chronic opiates administration. Present project will apply a multidisciplinary approach, combining state-of the art biophysical, pharmacological and real time video-imaging techniques to significantly extend current knowledge on the molecular and cellular mechanisms of cannabinoid/opioid-dependent alterations of synaptic plasticity in the hippocampus. These new theoretical knowledge can lay foundations for designing fundamentally novel clinical treatments for memory loss associated with cannabinoid/opioid addictions. In summary, the project will provide important added value both for basic science (learning and memory mechanisms), pharmacology (mechanisms of opioid/cannabinoid action on central neurones) and for biomedical research in the socially important field of drug abuse, addiction and their consequences.
Fields of science (EuroSciVoc)
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
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Coordinator
MANCHESTER
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.