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Opioid systems in the dentate gyrus
Carrie T Drake1, Charles Chavkin, Teresa A Milner
1Division of Neurobiology, Department of Neurology and Neuroscience, Weill-Cornell Medical College, 411 East 69th Street, New York, NY 10021, USA.
Progress in Brain Research
|September 4, 2007
Summary
Opiate drugs impact brain function, particularly the hippocampus. Opioid peptides like enkephalins and dynorphins, acting on specific receptors, have opposing effects on neural excitability and long-term potentiation (LTP).
Area of Science:
- Neuroscience
- Neuropharmacology
- Cellular and Molecular Biology
Background:
- Opiate drugs significantly affect cognitive functions and hippocampal excitability.
- The dentate gyrus (DG) in the hippocampus features enkephalins and dynorphins with contrasting roles in neural excitability.
- Opioid receptors, including delta- (DORs), mu- (MORs), and kappa- (KORs), are modulated by both endogenous peptides and exogenous opiates.
Purpose of the Study:
- To elucidate the distinct roles of enkephalins and dynorphins in modulating hippocampal excitability.
- To investigate the differential effects of MOR, DOR, and KOR activation on hippocampal function, including long-term potentiation (LTP).
- To explore the broader impact of opiates and opioids on hippocampal processes such as neurogenesis and development.
Main Methods:
- Review of anatomical and physiological evidence detailing opioid peptide and receptor localization within the hippocampus.
- Analysis of studies examining the effects of opioid receptor agonists on hippocampal excitability and LTP induction.
- Synthesis of recent findings on opioid modulation of neurogenesis, hormonal actions, and developmental systems.
Main Results:
- Enkephalins, binding to DORs and MORs, are found in GABAergic interneurons and increase hippocampal excitability and LTP.
- Dynorphins, binding to KORs, are located in granule cells and mossy fibers, and their activation diminishes LTP induction.
- Opioid receptors are strategically located on interneurons and afferents, influencing synaptic transmission and plasticity.
Conclusions:
- Endogenous opioid peptides and exogenous opiates exert complex, often opposing, modulatory effects on hippocampal excitability and synaptic plasticity.
- Differential localization and receptor binding of enkephalins and dynorphins underlie their distinct influences on hippocampal function.
- Opioids represent a critical regulatory system within the hippocampus, impacting diverse processes from neuronal excitability to adult neurogenesis.
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