Journal of Neurophysiology, Vol 76, Issue 3 1559-1565, Copyright © 1996 by APS

ARTICLES

Forskolin enhancement of opioid currents in rat locus coeruleus neurons

P. B. Osborne and J. T. Williams
Vollum Institute, Oregon Health Science University, Portland 97201, USA.

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 approximately 30% of control measured at -60 mV. This effect of forskolin was dependent on the concentration having a threshold of approximately 1 microM and a peak effect at approximately 30 microM. Dideoxyforskolin (30 microM) caused a small reduction (-52 +/- 28 pA, mean +/- SE) in the amplitude of the opioid current. 3. Forskolin increased the agonist current in the outward direction over the entire potential range between -140 and -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. Both the forskolin augmentation of the opioid current and the opoid current itself were reduced when the space clamp was improved by cutting the slice in the coronal plane, increasing the extracellular potassium concentration, and treating the slice with carbenoxolone. In addition, forskolin did not change the reversal potential of the opoid current. When expressed as a percentage change from control, forskolin had no significant effect on the opioid current in carbenoxolone (-13 +/- 13%) but produced a small augmentation in high extracellular potassium (15 +/- 4%) and coronoal slices (31 +/- 12%). 5. Two models were tested to explain the action of forskolin, one where cells are coupled electronically by a forskolin-sensitive conductance (coupled-cell model) and a second where opioids mediate an inhibition of a forskolin-induced cation conductance (2-conductance model). The experimental results were fit well 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.

This article has been cited by other articles:

				J. Verweij, E. P. Hornstein, and J. L. Schnapf Surround Antagonism in Macaque Cone Photoreceptors J. Neurosci., November 12, 2003; 23(32): 10249 - 10257. [Abstract] [Full Text] [PDF]

				M. Torrecilla, C. L. Marker, S. C. Cintora, M. Stoffel, J. T. Williams, and K. Wickman G-Protein-Gated Potassium Channels Containing Kir3.2 and Kir3.3 Subunits Mediate the Acute Inhibitory Effects of Opioids on Locus Ceruleus Neurons J. Neurosci., June 1, 2002; 22(11): 4328 - 4334. [Abstract] [Full Text] [PDF]

				S. Akbarian, M. Rios, R.-J. Liu, S. J. Gold, H.-F. Fong, S. Zeiler, V. Coppola, L. Tessarollo, K. R. Jones, E. J. Nestler, et al. Brain-Derived Neurotrophic Factor Is Essential for Opiate-Induced Plasticity of Noradrenergic Neurons J. Neurosci., May 15, 2002; 22(10): 4153 - 4162. [Abstract] [Full Text] [PDF]

				V. A. Alvarez, C. C. Chow, E. J. Van Bockstaele, and J. T. Williams Frequency-dependent synchrony in locus ceruleus: Role of electrotonic coupling PNAS, March 19, 2002; 99(6): 4032 - 4036. [Abstract] [Full Text] [PDF]

				A. Ivanov and G. Aston-Jones Local Opiate Withdrawal in Locus Coeruleus Neurons In Vitro J Neurophysiol, June 1, 2001; 85(6): 2388 - 2397. [Abstract] [Full Text] [PDF]

				M. Kamermans, I. Fahrenfort, K. Schultz, U. Janssen-Bienhold, T. Sjoerdsma, and R. Weiler Hemichannel-Mediated Inhibition in the Outer Retina Science, May 11, 2001; 292(5519): 1178 - 1180. [Abstract] [Full Text]

				A. Peinado Immature Neocortical Neurons Exist as Extensive Syncitial Networks Linked by Dendrodendritic Electrical Connections J Neurophysiol, February 1, 2001; 85(2): 620 - 629. [Abstract] [Full Text] [PDF]

				J. T. Williams, M. J. Christie, and O. Manzoni Cellular and Synaptic Adaptations Mediating Opioid Dependence Physiol Rev, January 1, 2001; 81(1): 299 - 343. [Abstract] [Full Text] [PDF]

				M. Usher, J. D. Cohen, D. Servan-Schreiber, J. Rajkowski, and G. Aston-Jones The Role of Locus Coeruleus in the Regulation of Cognitive Performance Science, January 22, 1999; 283(5401): 549 - 554. [Abstract] [Full Text]

				D. I. Vaney, J. C. Nelson, and D. V. Pow Neurotransmitter Coupling through Gap Junctions in the Retina J. Neurosci., December 15, 1998; 18(24): 10594 - 10602. [Abstract] [Full Text] [PDF]