OPIOID INHIBITION IN LOCUS-COERULEUS

1. Inhibition of locus coeruleus (LC) neurons by opioids is mediated b y hyperpolarization associated with an increase in potassium conductan ce. 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. Wh ole cell and intracellular recording were made from LC neurons in the slice preparation and currents were measured with a switch clamp ampli fier. 3. Local application of [Met](5) enkephalin (ME) by iontophoresi s resulted in two different effects depending on the site of applicati on. Iontophoresis of ME close to the cell caused an outward current th at reversed polarity near the potassium equilibrium potential. Whereas application at a distance >200 mu m resulted in an outward current th at did not reverse polarity even at strongly negative potentials. 4. W hen potassium conductances were blocked with internal Cs and/or extern al Ba, the opioid current was reduced to <15% of control. 5. Low sodiu m solutions were used to reduce sodium-dependent conductances. These s olutions hyperpolarized LC neurons themselves, decreased outward curre nts caused by ME, and shifted the reversal potential of the ME induced current to less negative values. 6. Electrotonic coupling of LC neuro ns 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 electroto nic coupling, had no effect on the action potential, spontaneous activ ity, or the resting conductance but blocked electrotonic coupling betw een 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 con sistent with the hypothesis that LC cells are electrotonically coupled . Such electrotonic coupling at the level of the nucleus locus coerule us would mediate synchronous regulation of noradrenaline in widespread areas of the brain.