Research Topic

The Emerging Role of Endocannabinoids in Synaptic Plasticity, Reward, and Addiction

About this Research Topic

Endocannabinoids (eCBs) are lipid signaling molecules that are synthesized on-demand and often work in a retrograde fashion. The most common eCBs are 2-arachidonoylglycerol (2-AG) and anandamide, which bind receptors such as cannabinoid receptor 1 (CB1), CB2, and transient receptor potential 1. ...

Endocannabinoids (eCBs) are lipid signaling molecules that are synthesized on-demand and often work in a retrograde fashion. The most common eCBs are 2-arachidonoylglycerol (2-AG) and anandamide, which bind receptors such as cannabinoid receptor 1 (CB1), CB2, and transient receptor potential 1. Endocannabinoid signaling controls numerous behaviors via actions throughout the central nervous system. However, much knowledge is lacking regarding how eCBs control synaptic plasticity in the mesolimbic reward system, including the ventral tegmental area (VTA) and nucleus accumbens (NAc), and how eCB-dependent plasticity contributes to the addiction cycle. Forms of synaptic plasticity, such as long-term depression (LTD) and long-term potentiation (LTP), are considered essential for normal reward learning and for maladaptive behaviors underlying drug abuse and addiction.

While certain types of LTP and LTD are dependent on eCB signaling, there is still the need to understand the mechanisms underlying eCB-dependent LTP and LTD promotion of reward and addiction.

Emerging technologies allow an unprecedented ability to study eCB system function and its contribution to behavior. For example, optogenetic approaches using light-sensitive proteins in genetically-defined cell types allow temporal-specific control of targeted neuronal populations in behaving animals. Thus optogenetic technology allows isolation of eCB involvement in a circuit-specific manner. Gene editing technologies, such as CRISPR-Cas9, offer another approach to identify the impact of specific eCB signaling components’ expression on neural function control. Finally, technological advances in fluorescent imaging allow rapid measures of genetically defined cell types and neurotransmitter systems during behavior.

Further elucidating how eCB signaling contributes to reward and addiction is especially pertinent given the recent legalization of medicinal or recreational marijuana throughout the world. The major psychoactive component in marijuana is THC, which acts on CB1R, the highest expressed GPCR in the brain with broad distribution. Common outputs of THC are behavioral changes including short-term memory loss, appetite stimulation, and reward.

There is still much to investigate, concerning THC use, particularly in adolescence, with a focus on long-term alterations in eCB system function and behavioral changes including the development of cannabis use disorder, depression risk, altered cognition, etc.

In this scenario, there is a need for further research clarifying how marijuana and similar CB1 targeting drugs implied in long-term brain alterations, affecting synaptic plasticity, are linked to addiction behaviors. This will allow for informed decisions regarding the legal, recreational, and medical use of marijuana.

This Research Topic aims to obtain an in-depth knowledge on eCBs role in synaptic plasticity affecting reward and addiction. To this aim, a focus on novel techniques’ application to study the impact on specific neural elements is necessary. Other drugs of abuse such as cocaine and opiates, should also be examined, as both are involved in the modulation of eCB system function and synaptic plasticity at the level of the reward circuit. Drugs of abuse modulating eCB-dependent forms of LTD and LTP are crucial to plasticity in reward circuits including the VTA and NAc.

We welcome submissions focusing on, but not limited to:

• Mesocorticolimbic reward system – eCB-dependent LTP and LTD – signaling at the synapse
• Novel techniques exploring eCBs’ role at the synapse -cellular and behavioral analysis
• Marijuana’s role in modulating reward/addiction
• Drug of abuse interaction with the eCB system: Mechanism and function
• eCB role in reward/addiction of carbohydrate and fat consumption


Keywords: Endocannabinoid, CB1, THC, Ventral Tegmental Area, LTP, LTD


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Submission Deadlines

29 January 2021 Manuscript
31 March 2021 Manuscript Extension

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

29 January 2021 Manuscript
31 March 2021 Manuscript Extension

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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