Forskolin enhancement of opioid currents in rat locus coeruleus neurons. Osborne, Peregrine B. and John T. Williams. Vollum Institute, Oregon Health Sciences University, Portland, OR 97201, USA.
APStracts 3:0079N, 1996.
1. Opioids are known to hyperpolarize all neurons in the nucleus locus coeruleus (LC) and to inhibit adenylyl cyclase. Recent work has shown that activation of adenylyl cyclase with forskolin increased the amplitude of the opioid hyperpolarization in LC cells. The aim of the present study was to determine the mechanism of this augmented hyperpolarization. 2. Agonist induced currents were studied in LC cells in brain slices using both intracellular and whole cell recordings. Forskolin increased the amplitude of [mu]-opioid and [alpha] 2 -adrenoceptor mediated currents by about 30% of control measured at -60 mV. This effect of forskolin was dependent on the concentration having a threshold of about 1 [mu]M and a peak effect at about 30 [mu]M. Dideoxyforskolin (30 [mu]M) caused a small reduction (-52+/-28 pA) in the amplitude of the opioid current. 3. Forskolin increased the agonist current in the outward direction over the entire potential range between -140 mV to -50 mV when recordings were made from neurons in cells recorded from slices cut in the horizontal plane. This augmented current produced a shift of the apparent reversal potential to more negative values. 4. The augmentation of the opioid current caused by forskolin was reduced from 142+/-27 pA when the space clamp was improved by cutting the slice in the coronal plane (to 45+/-13 pA), increasing the extracellular potassium concentration (to 29+/-9 pA), or treating the slice with carbenoxolone (to -12+/-6 pA). Thus forskolin did not directly augment the opioid induced conductance. 5. Two models were tested to explain the action of forskolin, one where cells are electrotonically coupled by a forskolin sensitive conductance (coupled cell model) and a second where opioids mediate an inhibition of a forskolin-induced cation conductance (two conductance model). The experimental results were well fit only by the coupled cell model which predicted that the opioid/forskolin interaction is indirect and occurs primarily in response to forskolin increasing the degree of electrotonic coupling between LC neurons. The consequence of increased coupling would be to augment synchronous activity within the nucleus.

Received 21 December 1995; accepted in final form 3 April 1996.
APS Manuscript Number J857-5.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 May 96