Opioids decrease high-voltage activated calcium currents in acutely dissociated neostriatal neurons

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.