Opioids In The Dentate Gyrus

Introduction:

Imagine sitting there and then suddenly an overwhelming sense of fear washes over you. All that is possible is sit there and be a distant spectator to your surroundings unable to interact for the moment. After seconds that feel like an eternity pass you then come to gaining back full awareness, but still lacking the ability to breathe or speak correctly. This is an example of what a seizure feels like and a significant portion of the population, about 1%, suffer from a condition known as epilepsy, or reoccurring seizures (10). To be considered an epileptic, seizures can be as frequent as twenty times a day or as rarely as once every several years. The frequency of these events can be based on a myriad of reasons, such as the

Since opioids are also known to affect seizure activity as well, opioids are looked in how they can be modulated in order to decrease seizure activity. Within the dentate gyrus (DG), there are two opioid peptides, enkephalins and dynorphins, which both have effects on excitability, but with contrasting effects (11). The difference between these two peptides is that enkephalins bind to delta- and mu- opioid receptors (DORs and MORs) whereas dynorphins bind to kappa-opioid receptors (KORs). However, unlike galanin receptors, opioid receptors can be activated by exogenous opiate drugs, which means that overdose can be possible because it is not reliant on an endogenous ligand. For example, the MOR agonist morphine can bind which means that a ligand can be introduced and not well regulated by the body, leading to overdose (11). Research has found that enkephalins are scattered in GABAergic interneurons, with MORs and DORs inhibit granule cells because they are in very distinct subpopulations of GABAergic interneurons (11). On the other hand, dynorphins are in granule cells and dendrites and KOR agonists, which will consist of endogenous dynorphins, decrease long-term potentiation. KORs have also been found to regulate GABA release at the presynaptic sites of the neurons (K- opioid). GABA, being the main inhibitory

Temporal lobe epilepsy is known to being resistant to medication, which is why current research is investigating how G- proteins can become activated by the mu opioid receptor selective peptide (DAMGO) and nociception (Temp Lobe G). Another aspect examined is the binding to mu and nociception (NOP) receptors and adenylyl cyclase (AC) in the neocortex, which is the region of the brain associated with temporal lobe epilepsy (Temp). By comparing the levels of [3H]DAMGO binding and stimulation, it was concluded that epileptics with temporal lobe seizure were found to have changes in the mu opioid and NOP receptor binding and, also, the downstream receptors were found to have alterations in their signal transduction mechanisms