Opioids can evoke direct receptor-mediated excitatory effects on sensory neurons

Crain, Stanley M.; Shen, Ke‐Fei

doi:10.1016/0165-6147(90)90322-y

Cited by 318 publications

(169 citation statements)

References 25 publications

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“…Several reports suggest that activation of opioid receptors could both inhibit and stimulate AC activity, depending on opioid agonist concentration. Opioid agonists at low concentrations activate Gs proteins and stimulate AC activity, while high concentrations of opioid agonists activate Gi and inhibit AC activity in myenteric plexus and dorsal root ganglion cells [16,17]. Using x-opioid receptor-transfected CHO cells, we found that low concentrations of U69593 (e.g.…”

Section: Discussionmentioning

confidence: 99%

κ‐Opioid receptor‐transfected cell lines: modulation of adenylyl cyclase activity following acute and chronic opioid treatments

et al. 1995

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Section: Discussionmentioning

confidence: 99%

κ‐Opioid receptor‐transfected cell lines: modulation of adenylyl cyclase activity following acute and chronic opioid treatments

et al. 1995

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“…Ca2+ conductances might also be altered. Opiates, including dynorphin A (Gross et al, 1990), can alter Ca'+ currents in several neuron types (Gross and MacDonald, 1987;Crain and Shen, 1990;Surprenant et al, 1990;Regan et al, 1991;Seward et al, 1991). Such a Ca'+ channel effect is interesting in the light of recent studies suggesting a role for intracellular Ca'-+ in the regulation of I, in sympathetic ganglia neurons (Beech et al,199 1;Kirkwood et al,199 1;Marrion et al,199 1).…”

Section: Hyperpolarizingmentioning

confidence: 99%

Voltage-dependent effects of opioid peptides on hippocampal CA3 pyramidal neurons in vitro

et al. 1994

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Opioid peptides, and especially the dynorphins, have been localized to several circuits in the CA3 hippocampal region, yet electrophysiological studies often find mixed effects of opiates on the excitability of CA3 neurons. Reasoning that these mixed effects might involve voltage-dependent actions, we tested the effect of several opiates on CA3 pyramidal neurons using single-electrode voltage-clamp recording in a slice preparation of rat hippocampus. In most CA3 neurons, the voltage-dependent K+ current known as the M-current (IM) was uniquely sensitive to the opioid peptides, with the direction of response dependent upon the opiate type and concentration. Thus, an opiate selective for kappa receptors, U-50,488H, significantly augmented IM. The kappa-selective agonists dynorphin A and dynorphin B, which exist in mossy fiber afferents to CA3 pyramidal neurons, also markedly augmented IM at low concentrations (20–100 nM). By contrast, dynorphin A at higher concentrations (1–1.5 microM) often reduced IM. Similarly, several opiates [e.g., D-Ala2,D-Leu5-enkephalin: (DADL), [D- Pen2,5]-enkephalin (DPDPE)] known to act on the delta receptor subtypes reduced the M-current, with partial reversal of this effect by naloxone. Neither the selective mu-receptor agonist [D-Ala2, NMe-Phe4, Gly-ol]-enkephalin (DAMGO) nor the nonopioid fragment of dynorphin, des- Tyr-dynorphin, consistently altered IM. These opiate effects on IM were accompanied by changes in conductance and holding current consistent with their respective effects on IM. Dynorphin A did not measurably affect the Q-current, a conductance known to contribute to inward rectification in hippocampal pyramidal neurons. The opiate effects on IM were not altered by pretreatment with Cs+ (which blocks IQ) or Ca2+ channel blockers. The opposing effects of the dynorphins (both A and B) and DADL on IM were antagonized by naloxone (1–3 microM), and the dynorphin-induced augmentations of IM were usually reversed by the kappa receptor antagonist norbinaltorphimine. These results suggest that the opiates can have opposing effects on the same voltage- dependent K+ channel type (the M channel) in the rat CA3 pyramidal neuron, with the direction of the response depending on which receptor subtype is activated. These data not only help explain the mixed effects of opiates seen in other studies, but also suggest a potential postsynaptic function for the endogenous opiates contained in the CA3 mossy fibers.

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“…General role for G-proteins and an upregulated CAMP system in opiate addiction Biochemical studies have thus demonstrated upregulation of the CAMP system in response to chronic opiate exposure in a number of discrete regions of the CNS in addition to the LC, including the dorsal root ganglion-spinal cord, nucleus accumbens (NAc), amygdala, and thalamus (Makman et al, 1988;Crain and Shen, 1990;Terwilliger et al, 199 1 a), indicating that upregulation of adenylate cyclase and CAMP-dependent protein kinase may represent a common mechanism by which a number of opiate-sensitive neurons adapt to chronic morphine administration. Among the regions that exhibit an upregulated CAMP system with chronic opiate administration, there are different types of changes in the levels of G-protein subunits: increased levels of reward that leads to compulsive drug use?…”

Section: Molecularmentioning

confidence: 99%

Molecular mechanisms of drug addiction [published erratum appears in J Neurosci 1992 Aug;12(8):following table of contents]

Ej¹

1992

J. Neurosci.

472

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Drug addiction has afflicted mankind for centuries, yet the mechanisms by which particular drugs lead to addiction, and the genetic factors that make some individuals particularly vulnerable to addiction, have remained elusive. From a clinical perspective, drug abuse continues to exact enormous human and financial costs on society, yet all currently available treatments for drug addiction are notoriously ineffective. The search for a better understanding of the neurobiological mechanisms underlying the addictive actions of drugs of abuse and of the genetic factors that contribute to addiction should be given a high priority, as this should result in crucial advances in our ability to treat and prevent drug addiction.From the basic neuroscience perspective, study of the neurobiology of drug addiction offers a novei opportunity to establish the biological basis of a complex and clinically relevant behavioral abnormality. Many prominent aspects of drug addiction in people can be clearly reproduced in laboratory animals, in striking contrast to most other forms of neuropsychiatric illness, such as psychotic and affective disorders, animal models for which are much harder to interpret. Advances made in the study of drug addiction should provide important insights into mechanisms underlying some of these other disorders.Three terms related to drug abuse are used commonly: tolerance, dependence, and addiction. Tolerance represents a reduced effect upon repeated exposure to a drug at a constant dose, or the need for an increased dose to maintain the same effect. Dependence is defined as the need for continued exposure to a drug so as to avoid a withdrawal syndrome (physical and/ or psychological disturbances) when the drug is withdrawn. Dependence is considered a priori to result from adaptive changes that develop in body tissues in response to repeated drug exposure. The traditional distinction between physical and psychological dependence is somewhat artificial, since both are mediated by neural mechanisms, possibly even similar neural mechanisms, as will be seen below. Addiction is defined as the compulsive use of a drug despite adverse consequences. In the I thank Drs.

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Opioids can evoke direct receptor-mediated excitatory effects on sensory neurons

Cited by 318 publications

References 25 publications

κ‐Opioid receptor‐transfected cell lines: modulation of adenylyl cyclase activity following acute and chronic opioid treatments

κ‐Opioid receptor‐transfected cell lines: modulation of adenylyl cyclase activity following acute and chronic opioid treatments

Voltage-dependent effects of opioid peptides on hippocampal CA3 pyramidal neurons in vitro

Molecular mechanisms of drug addiction [published erratum appears in J Neurosci 1992 Aug;12(8):following table of contents]

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