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Opioids decrease high-voltage activated calcium currents in acutely dissociated neostriatal neurons
A Stefani1, D J Surmeier, G Bernardi
1Clinica Neurologica, Università di Roma Tor Vergata, Italy.
Abstract:
Although the distribution of opioid receptors is central to the patch-matrix model of neostriatal organization, it has been unclear whether these receptors are located post-synaptically. Moreover, it has not yet been clarified whether opioid receptor activation in neostriatum results in the modulation of calcium and/or potassium conductances. To test this, neostriatal neurons were acutely isolated and their sensitivity to opioid receptor agonists determined. At nanomolar concentrations, both the mu-agonist [D-Ala2, MePhe4,Gly-ol5]-enkephalin (DAMGO) and the delta-agonist [D-Pen2, D-Pen5]-enkephalin (DPEPE) reversibly decreased whole-cell calcium currents in medium-sized neurons. These effects were blocked by the opiate antagonist naloxone. These findings argue that activation of post-synaptic, opioid receptors is capable of modulating the excitability of neostriatal neurons.
Insights
Opioid receptors in the neostriatum are located post-synaptically. Their activation by agonists like DAMGO and DPEPE modulates calcium currents in medium-sized neurons, affecting neuronal excitability.
Area of Science:
- Neuroscience
- Neuropharmacology
Background:
- The patch-matrix model of neostriatal organization relies on opioid receptor distribution.
- The precise location (pre- vs. post-synaptic) of these receptors and their functional impact on ion conductances remain unclear.
Purpose of the Study:
- To determine if opioid receptors in the neostriatum are post-synaptically located.
- To investigate whether opioid receptor activation modulates calcium and/or potassium conductances in neostriatal neurons.
Main Methods:
- Acutely isolated neostriatal neurons were used to assess sensitivity to opioid receptor agonists.
- Whole-cell patch-clamp electrophysiology was employed to measure calcium currents.
Main Results:
- Both mu-agonist DAMGO and delta-agonist DPEPE significantly decreased whole-cell calcium currents in medium-sized neostriatal neurons at nanomolar concentrations.
- These inhibitory effects on calcium currents were reversed by the opiate antagonist naloxone.
- Potassium conductances were not explicitly mentioned as modulated in this abstract.
Conclusions:
- These findings support the presence of functional, post-synaptic opioid receptors in the neostriatum.
- Activation of these post-synaptic opioid receptors can modulate neuronal excitability by altering calcium conductances.