Opioid inhibition in locus coeruleus

1. Inhibition of locus coeruleus (LC) neurons by opioids is mediated by hyperpolarization associated with an increase in potassium conductance. However, opioids caused an outward current even at potentials more negative than the potassium equilibrium potential in the majority of LC neurons recorded in brain slices cut in the horizontal plane. 2. Whole cell and intracellular recording were made from LC neurons in the slice preparation and currents were measured with a switch clamp amplifier. 3. Local application of [Met]⁵enkephalin (ME) by iontophoresis resulted in two different effects depending on the site of application. Iontophoresis of ME close to the cell caused an outward current that reversed polarity near the potassium equilibrium potential. Whereas application at a distance >200 μm resulted in an outward current that did not reverse polarity even at strongly negative potentials. 4. When potassium conductances were blocked with internal Cs and/or external Ba, the opioid current was reduced to <15% of control. 5. Low sodium solutions were used to reduce sodium-dependent conductances. These solutions hyperpolarized LC neurons themselves, decreased outward currents caused by ME, and shifted the reversal potential of the ME induced current to less negative values. 6. Electrotonic coupling of LC neurons in neonatal animals is thought to synchronize spontaneous activity. In this study, synchronous activity in cells from adult animals also was observed, suggesting that electrotonic coupling in the LC persists into adulthood. 7. Carbenoxolone, an agent thought to block electrotonic coupling, had no effect on the action potential, spontaneous activity, or the resting conductance but blocked electrotonic coupling between LC neurons in neonates, blocked synchronous activity in LC neurons from adult animals, and shifted the reversal potential of the opioid current to the potassium equilibrium potential. 8. All results are consistent with the hypothesis that LC cells are electrotonically coupled. Such electrotonic coupling at the level of the nucleus locus coeruleus would mediate synchronous regulation of noradrenaline in widespread areas of the brain.