Opioid Tolerance/Dependence in Sensory Neuron Cultures

Crain, Stanley M.

Abstract

Electrophysiologic studies indicate that excitatory opioid receptors on mouse sensory dorsal-root ganglion (DRG) neurons in culture are positively coupled via Gs to cyclic AMP-dependent voltage-sensitive ion channels. After chronic opioid exposure of DRG/spinal cord explants the DRG neurons become tolerant to the acute inhibitory (action potential-shortening) effects of high (uM) concentrations of opioids and remarkably sensitive to the excitatory (action potential-prolonging) effects of low (

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute on Drug Abuse (NIDA)
• Type: Research Project (R01)
• Project #: 2R01DA002031-13
• Application #: 2116490
• Study Section: Drug Abuse Biomedical Research Review Committee (DABR)
• Project Start: 1978-07-01
• Project End: 1994-02-28
• Budget Start: 1992-03-15
• Budget End: 1994-02-28
• Support Year: 13
• Fiscal Year: 1992

Institution

• Name: Albert Einstein College of Medicine
• Department: Neurosciences
• Type: Schools of Medicine
• DUNS #: 009095365
• City: Bronx
• State: NY
• Country: United States
• Zip Code: 10461

Publications

Shen, K F; Crain, S M (1994) Nerve growth factor rapidly prolongs the action potential of mature sensory ganglion neurons in culture, and this effect requires activation of Gs-coupled excitatory kappa-opioid receptors on these cells. J Neurosci 14:5570-9

Shen, K F; Crain, S M (1994) Antagonists at excitatory opioid receptors on sensory neurons in culture increase potency and specificity of opiate analgesics and attenuate development of tolerance/dependence. Brain Res 636:286-97

Cruciani, R A; Dvorkin, B; Klinger, H P et al. (1994) Presence in neuroblastoma cells of a mu 3 receptor with selectivity for opiate alkaloids but without affinity for opioid peptides. Brain Res 667:229-37

Cruciani, R A; Dvorkin, B; Morris, S A et al. (1993) Direct coupling of opioid receptors to both stimulatory and inhibitory guanine nucleotide-binding proteins in F-11 neuroblastoma-sensory neuron hybrid cells. Proc Natl Acad Sci U S A 90:3019-23

Fan, S F; Shen, K F; Crain, S M (1993) mu and delta opioid agonists at low concentrations decrease voltage-dependent K+ currents in F11 neuroblastoma x DRG neuron hybrid cells via cholera toxin-sensitive receptors. Brain Res 605:214-20

Crain, S M; Shen, K F (1992) After GM1 ganglioside treatment of sensory neurons naloxone paradoxically prolongs the action potential but still antagonizes opioid inhibition. J Pharmacol Exp Ther 260:182-6

Shen, K F; Crain, S M (1992) Chronic selective activation of excitatory opioid receptor functions in sensory neurons results in opioid 'dependence' without tolerance. Brain Res 597:74-83

Crain, S M; Shen, K F (1992) After chronic opioid exposure sensory neurons become supersensitive to the excitatory effects of opioid agonists and antagonists as occurs after acute elevation of GM1 ganglioside. Brain Res 575:13-24

Fan, S F; Shen, K F; Scheideler, M A et al. (1992) F11 neuroblastoma x DRG neuron hybrid cells express inhibitory mu- and delta-opioid receptors which increase voltage-dependent K+ currents upon activation. Brain Res 590:329-33

Terwilliger, R Z; Beitner-Johnson, D; Sevarino, K A et al. (1991) A general role for adaptations in G-proteins and the cyclic AMP system in mediating the chronic actions of morphine and cocaine on neuronal function. Brain Res 548:100-10