Skip to main content
SpringerLink
Log in

Protein kinase C isozymes and addiction

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Protein kinase C (PKC) has long been recognized an important family of enzymes that regulate numerous aspects of neuronal signal transduction, neurotransmitter synthesis, release and reuptake, receptor and ion channel function, neuronal excitability, development, and gene expression. Much evidence has implicated PKCs in the effects of several drugs of abuse, and in behavioral responses to these drugs. The present review summarizes the effects of both acute and chronic exposure to various drugs of abuse on individual PKC isozymes in the brain. In addition, we summarize recent studies utilizing mice with targeted deletions of the genes for PKCγ and PKCɛ. These studies suggest that individual PKC isozymes play a role in the development of drug dependence and addiction.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Nishizuka Y. (2001). The protein kinase c family and lipid mediators for transmembrane signaling and cell regulation. Alcohol. Clin. Exp. Res. 25, 3S-7S.

    PubMed  CAS  Google Scholar 

  2. Nishizuka Y. (1988). The molecular heterogeneity of protein kinase C and its implications for cellular regulation. Nature 334, 661–665.

    Article  PubMed  CAS  Google Scholar 

  3. Mellor H., and Parker P. J. (1998). The extended protein kinase C superfamily. Biochem. J. 332 (Pt 2), 281–292.

    PubMed  CAS  Google Scholar 

  4. Rykx A., De Kimpe L., Mikhalap S., Vantus T., Seufferlein T., Vandenheede J. R., and Van Lint J. (2003). Protein kinase D: a family affair. FEBS Lett. 546, 81–86.

    Article  PubMed  CAS  Google Scholar 

  5. Fisher S. K., Heacock A. M., and Agranoff B. W. (1992). Inositol lipids and signal transduction in the nervous system—an update. J. Neurochem. 58, 18–38.

    Article  PubMed  CAS  Google Scholar 

  6. Nishizuka Y. (1995). Protein kinase C and lipid signaling for sustained cellular responses. FASEB J. 9, 484–496.

    PubMed  CAS  Google Scholar 

  7. Murakami K., Chan S. Y., and Routtenberg A. (1986). Protein kinase C activation by cis-fatty acid in the absence of Ca2+ and phospholipids. J. Biol. Chem. 261, 15,424–15,429.

    CAS  Google Scholar 

  8. Shinomura T., Asaoka Y., Oka M., Yoshida K., and Nishizuka Y. (1991). Synergistic action of diacylglycerol and unsaturated fatty acid for protein kinase C activation: its possible implications. Proc. Natl. Acad. Sci. USA 88, 5149–5153.

    Article  PubMed  CAS  Google Scholar 

  9. Toker A., Meyer M., Reddy K. K., et al. (1994). Activation of protein kinase C family members by the novel polyphosphoinositides PtdIns-3,4-P2 and PtdIns-3,4,5-P3. J. Biol. Chem. 269, 32,358–32,367.

    CAS  Google Scholar 

  10. Parekh D. B., Ziegler W., and Parker P. J. (2000). Multiple pathways control protein kinase C phosphorylation. EMBO J. 19, 496–503.

    Article  PubMed  CAS  Google Scholar 

  11. Toker A. (2002). Phosphoinositides and signal transduction. Cell. Mol. Life Sci. 59, 761–779.

    Article  PubMed  CAS  Google Scholar 

  12. Minami H., Owada Y., Handa Y., and Kondo H. (2001). Localization of mRNAs for novel, atypical as well as conventional protein kinase C (PKC) isoforms in the brain of developing and mature rats. J. Mol. Neurosci. 15, 121–135.

    Article  Google Scholar 

  13. Naik M. U., Benedikz E., Hernandez I., et al. (2000). Distribution of protein kinase Mζ and the complete protein kinase C isoform family in rat brain. J. Comp. Neurol. 426, 243–258.

    Article  PubMed  CAS  Google Scholar 

  14. Young W. S. III (1988). Expression of three (and a putative four) protein kinase C genes in brains of rat and rabbit. J. Chem. Neuroanat. 1, 177–194.

    PubMed  CAS  Google Scholar 

  15. Huang F. L., Yoshida Y., Nakabayashi H., Young W. S. 3d., and Huang K. P. (1988). Immunocytochemical localization of protein kinase C isozymes in rat brain. J. Neurosci. 8, 4734–4744.

    PubMed  CAS  Google Scholar 

  16. Tanaka C. and Saito N. (1992). Localization of subspecies of protein kinase C in the mammalian central nervous system. Neurochem. Intl. 21, 499–512.

    Article  CAS  Google Scholar 

  17. American Psychiatric Association. (1994). Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. American Psychiatric Press, Arlington, VA.

    Google Scholar 

  18. Koob G. F. and Nestler E. J. (1997). The neurobiology of drug addiction. J. Neuropsychiatry Clin. Neurosci. 9, 482–497.

    PubMed  CAS  Google Scholar 

  19. Nestler E. J. (2001). Molecular basis of long-term plasticity underlying addiction. Nature Rev. Neurosci. 2, 119–128.

    Article  CAS  Google Scholar 

  20. Self D. W. (1998). Neural substrates of drug craving and relapse in drug addiction. Ann. Med. 30, 379–389.

    PubMed  CAS  Google Scholar 

  21. Slater S. J., Cox K. J., Lombardi J. V., Ho C., Kelly M. B., Rubin E., and Stubbs C. D. (1993). Inhibition of protein kinase C by alcohols and anaesthetics. Nature 364, 82–84.

    Article  PubMed  CAS  Google Scholar 

  22. Slater S. J., Kelly M. B., Larkin J. D., et al. (1997). Interaction of alcohols and anesthetics with protein kinase Cα. J. Biol. Chem. 272, 6167–6173.

    Article  PubMed  CAS  Google Scholar 

  23. Machu T. K., Olsen R. W., and Browning M. D. (1991). Ethanol has no effect on cAMP-dependent protein kinase-, protein kinase C-, or Ca2+-calmodulin-dependent protein kinase II-stimulated phosphorylation of highly purified substrates in vitro. Alcohol. Clin. Exp. Res. 15, 1040–1044.

    Article  PubMed  CAS  Google Scholar 

  24. Messing R. O., Petersen P. J., and Henrich C. J. (1991). Chronic ethanol exposure increases levels of protein kinase C δ and ɛ and protein kinase C-mediated phosphorylation in cultured neural cells. J. Biol. Chem. 266, 23,428–23,432.

    CAS  Google Scholar 

  25. Skwish S. and Shain W. (1990). Ethanol and diolein stimulate PKC translocation in astroglial cells. Life Sci. 47, 1037–1042.

    Article  PubMed  CAS  Google Scholar 

  26. Gordon A. S., Yao L., Wu Z. L., Coe I. R., and Diamond I. (1997). Ethanol alters the subcellular localization of δ and ɛ protein kinase C in NG108-15 cells. Mol. Pharmacol. 52, 554–559.

    PubMed  CAS  Google Scholar 

  27. McMahon T., Andersen R., Metten P., Crabbe J. C., and Messing R. O. (2000). Protein kinase C ɛ mediates up-regulation of N-type calcium channels by ethanol. Mol. Pharmacol. 57, 53–58.

    PubMed  CAS  Google Scholar 

  28. Hundle B., McMahon T., Dadgar J., Chen C. H., Mochly-Rosen D., and Messing R. O. (1997). An inhibitory fragment derived from protein kinase C ɛ prevents enhancement of nerve growth factor responses by ethanol and phorbol esters. J. Biol. Chem. 272, 15,028–15,035.

    Article  CAS  Google Scholar 

  29. Roivainen R., McMahon T., and Messing R. O. (1993). Protein kinase C isozymes that mediate enhancement of neurite outgrowth by ethanol and phorbol esters in PC12 cells. Brain Res. 624, 85–93.

    Article  PubMed  CAS  Google Scholar 

  30. Walter H. J., McMahon T., Dadgar J., Wang D., and Messing R. O. (2000). Ethanol regulates calcium channel subunits by protein kinase C δ-dependent and -independent mechanisms. J. Biol. Chem. 275, 25,717–25,722.

    CAS  Google Scholar 

  31. Gerstin E. H., McMahon T., Dadgar J., and Messing R. O. (1998). Protein kinase C δ mediates ethanol-induced up-regulation of L-type calcium channels. J. Biol. Chem. 273, 16,409–16,414.

    Article  CAS  Google Scholar 

  32. Pandey S. C., Dwivedi Y., Piano M. R., Schwertz D. W., Davis J. M., and Pandey G. N. (1993). Chronic ethanol-consumption decreases the phorbol ester binding to membranal but not cytosolic protein kinase C in rat brain. Alcohol 10, 259–262.

    Article  PubMed  CAS  Google Scholar 

  33. Battaini F., Delvesco R., Govoni S., and Trabucchi M. (1989). Chronic alcohol intake modifies phorbol ester binding in selected rat brain areas. Alcohol 6, 169–172.

    Article  PubMed  CAS  Google Scholar 

  34. Kruger H., Wilce P. A., and Shanley B. C. (1993). Ethanol and protein kinase C in rat brain. Neurochem. Intl. 22, 575–581.

    Article  CAS  Google Scholar 

  35. Pascale A., Battaini F., Govoni S., Persichella M., DeSalvia M. A., and Cuomo V. (1997). Chronic low doses of ethanol affect brain protein kinase C and ultrasonic calls in rats. Alcohol 14, 557–561.

    Article  PubMed  CAS  Google Scholar 

  36. Narita M., Tamaki H., Kobayashi M., Soma M., and Suzuki T. (2001). Changes in Ca2+-dependent protein kinase C isoforms induced by chronic ethanol treatment in mice. Neurosci. Lett. 307, 85–88.

    Article  PubMed  CAS  Google Scholar 

  37. McIntyre T. A., Souder M. G., Hartl M. W., and Shibley I. A. (1999). Ethanol-induced decrease of developmental PKC isoform expression in the embryonic chick brain. Dev. Brain. Res. 117, 191–197.

    Article  CAS  Google Scholar 

  38. Mahadev K. and Vemuri M. C. (1998). Selective changes in protein kinase C isoforms and phosphorylation of endogenous substrate proteins in rat cerebral cortex during pre- and postnatal ethanol exposure. Arch. Biochem. Biophys. 356, 249–257.

    Article  PubMed  CAS  Google Scholar 

  39. Allan A. and Harris R. (1987). Acute and chronic ethanol treatments alter GABA receptor-operated chloride channels. Pharmacol. Biochem. Behav. 27, 665–670.

    Article  PubMed  CAS  Google Scholar 

  40. Mehta A. K. and Ticku M. K. (1988). Ethanol potentiation of GABAergic transmission in cultured spinal cord neurons involves γ-aminobutyric acidA-gated chloride channels. J. Pharmacol. Exp. Ther. 246, 558–564.

    PubMed  CAS  Google Scholar 

  41. Suzdak P. D., Schwartz R. D., Skolnick P., and Paul S. M. (1986). Ethanol stimulates γ-aminobutyric acid receptor-mediated chloride transport in rat brain synaptoneurosomes. Proc. Natl. Acad. Sci. USA 83, 4071–4075.

    Article  PubMed  CAS  Google Scholar 

  42. Moss S. J. and Smart T. G. (1996). Modulation of amino acid-gated ion channels by protein phosphorylation. Intl. Rev. Neurobiol. 39, 1–52.

    Article  CAS  Google Scholar 

  43. Weiner J. L., Valenzuela C. F., Watson P. L., Frazier C. J., and Dunwiddie T. V. (1997). Elevation of basal protein kinase C activity increases ethanol sensitivity of GABAA receptors in rat hippocampal CA1 pyramidal neurons. J. Neurochem. 68, 1949–1959.

    Article  PubMed  CAS  Google Scholar 

  44. Weiner J. L., Zhang L., and Carlen P. L. (1994). Potentiation of GABAA-mediated synaptic current by ethanol in hippocampal CA1 neurons: possible role of protein kinase C. J. Pharmacol. Exp. Ther. 268, 1388–1395.

    PubMed  CAS  Google Scholar 

  45. Kumar S., Sieghart W., and Morrow A. L. (2002). Association of protein kinase C with GABAA receptors containing α1 and α4 subunits in the cerebral cortex: selective effects of chronic ethanol consumption. J. Neurochem. 82, 110–117.

    Article  PubMed  CAS  Google Scholar 

  46. Jiang Z. L. and Ye J. -H. (2003). Protein kinase Cɛ is involved in ethanol potentiation of glycine-gated Cl− current in rat neurons of ventral tegmental area. Neuropharmacology 44, 493–502.

    Article  PubMed  CAS  Google Scholar 

  47. Swerdlow N. R., Vaccarino F. J., Amalric M., and Koob G. F. (1986). The neural substrates for the motor-activating properties of psychostimulants: a review of recent findings. Pharmacol. Biochem. Behav. 25, 233–248.

    Article  PubMed  CAS  Google Scholar 

  48. Johanson C. E. and Fischman M. W. (1989). The pharmacology of cocaine related to its abuse. Pharmacol. Rev. 41, 3–52.

    PubMed  CAS  Google Scholar 

  49. Gold L. H., Geyer M. A., and Koob G. F. (1989). Neurochemical mechanisms involved in behavioral effects of amphetamines and related designer drugs. NIDA Res. Monogr. 94, 101–126.

    PubMed  CAS  Google Scholar 

  50. Browman K. E., Kantor L., Richardson S., Badiani A., Robinson T. E., and Gnegy M. E. (1998). Injection of the protein kinase C inhibitor Ro31-8220 into the nucleus accumbens attenuates the acute response to amphetamine: tissue and behavioral studies. Brain Res. 814, 112–119.

    Article  PubMed  CAS  Google Scholar 

  51. Kantor L. and Gnegy M. E. (1998). Protein kinase C inhibitors block amphetamine-mediated dopamine release in rat striatal slices. J. Pharmacol. Exp. Ther. 284, 592–598.

    PubMed  CAS  Google Scholar 

  52. Cervo L., Mukherjee S., Bertaglia A., and Samanin R. (1997). Protein kinases A and C are involved in the mechanisms underlying consolidation of cocaine place conditioning. Brain Res. 775, 30–36.

    Article  PubMed  CAS  Google Scholar 

  53. Steketee J. D. (1993). Injection of the protein kinase inhibitor H7 into the A10 dopamine region blocks the acute responses to cocaine: behavioral and in vivo microdialysis studies. Neuropharmacology 32, 1289–1297.

    Article  PubMed  CAS  Google Scholar 

  54. Steketee J. D. (1997). Intra-ventral tegmental area administration of H7 delays, but does not prevent the development of cocaine-induced sensitization. Brain Res. Bull. 43, 565–571.

    Article  PubMed  CAS  Google Scholar 

  55. Steketee J. D. (1994). Intra-A10 injection of H7 blocks the development of sensitization to cocaine. Neuroreport 6, 69–72.

    Article  PubMed  CAS  Google Scholar 

  56. Reith M. E., Xu C., and Chen N. H. (1997). Pharmacology and regulation of the neuronal dopamine transporter. Eur. J. Pharmacol. 324, 1–10.

    Article  PubMed  CAS  Google Scholar 

  57. Micheau J. and Riedel G. (1999). Protein kinases: which one is the memory molecule? Cell. Mol. Life Sci. 55, 534–548.

    Article  PubMed  CAS  Google Scholar 

  58. Fagnou D. D. and Tuchek J. M. (1995). The biochemistry of learning and memory. Mol. Cell. Biochem. 149-150, 279–286.

    Article  PubMed  CAS  Google Scholar 

  59. Nogues X. (1997). Protein kinase C, learning and memory: a circular determinism between physiology and behaviour. Prog. Neuropsychopharmacol. Biol. Psychiatry 21, 507–529.

    Article  PubMed  CAS  Google Scholar 

  60. Van der Zee E. A. and Douma B. R. (1997). Historical review of research on protein kinase C in learning and memory. Prog. Neuropsychopharmacol. Biol. Psychiatry 21, 379–406.

    Article  PubMed  Google Scholar 

  61. Thomas K. L. and Everitt B. J. (2001). Limbic-cortical-ventral striatal activation during retrieval of a discrete cocaine-associated stimulus: a cellular imaging study with γ protein kinase C expression. J. Neurosci. 21, 2526–2535.

    PubMed  CAS  Google Scholar 

  62. Van der Zee E. A., Luiten P. G., and Disterhoft J. F. (1997). Learning-induced alterations in hippocampal PKC-immunoreactivity: a review and hypothesis of its functional significance. Prog. Neuropsychopharmacol. Biol. Psychiatry 21, 531–572.

    Article  PubMed  Google Scholar 

  63. Van der Zee E. A., Kronforst-Collins M. A., Maizels E. T., Hunzicker-Dunn M., and Disterhoft J. F. (1997). γ Isoform-selective changes in PKC immunoreactivity after trace eyeblink conditioning in the rabbit hippocampus. Hippocampus 7, 271–285.

    Article  PubMed  Google Scholar 

  64. Abeliovich A., Chen C., Goda Y., Silva A. J., Stevens C. F., and Tonegawa S. (1993). Modified hippocampal long-term potentiation in PKC γ-mutant mice. Cell 75, 1253–1262.

    Article  PubMed  CAS  Google Scholar 

  65. Abeliovich A., Paylor R., Chen C., Kim J. J., Wehner J. M., and Tonegawa S. (1993). PKC γ mutant mice exhibit mild deficits in spatial and contextual learning. Cell 75, 1263–1271.

    Article  PubMed  CAS  Google Scholar 

  66. Van der Zee E. A., Compaan J. C., de Boer M., and Luiten P. G. (1992). Changes in PKC γ immunoreactivity in mouse hippocampus induced by spatial discrimination learning. J. Neurosci. 12, 4808–4815.

    PubMed  Google Scholar 

  67. Douma B. R., Van der Zee E. A., and Luiten P. G. (1998). Translocation of protein kinase Cγ occurs during the early phase of acquisition of food rewarded spatial learning. Behav. Neurosci. 112, 496–501.

    Article  PubMed  CAS  Google Scholar 

  68. Steketee J. D. (1997). Cocaine-induced behavioral sensitization is associated with increased protein kinase C activity in the ventral tegmental area. Neurosci. Res. Comm. 20, 59–67.

    Article  CAS  Google Scholar 

  69. Steketee J. D., Rowe L. A., and Chandler L. J. (1998). The effects of acute and repeated cocaine injections on protein kinase C activity and isoform levels in dopaminergic brain regions. Neuropharmacology 37, 339–347.

    Article  PubMed  CAS  Google Scholar 

  70. Freeman W. M., Brebner K., Lynch W. J., Patel K. M., Robertson D. J., Roberts D. C. S., and Vrana K. E. (2002). Changes in rat frontal cortex gene expression following chronic cocaine. Mol. Brain Res. 104, 11–20.

    Article  PubMed  CAS  Google Scholar 

  71. Kramer H. K., Poblete J. C., and Azmitia E. C. (1995). 3,4-Methylenedioxymethamphetamine (“Ecstasy”) promotes the translocation of protein kinase C (PKC): requirement of viable serotonin nerve terminals. Brain Res. 680, 1–8.

    Article  PubMed  CAS  Google Scholar 

  72. Kramer H. K., Poblete J. C., and Azmitia E. C. (1997). Activation of protein kinase C (PKC) by 3,4-methylenedioxymethamphetamine (MDMA) occurs through the stimulation of serotonin receptors and transporter. Neuropsychopharmacology 17, 117–129.

    Article  PubMed  CAS  Google Scholar 

  73. Kramer H. K., Poblete J. C., and Azmitia E. C. (1998). Characterization of the translocation of protein kinase C (PKC) by 3,4-methylenedioxymethamphetamine (MDMA/ecstasy) in synaptosomes: evidence for a presynaptic localization involving the serotonin transporter (SERT). Neuropsychopharmacology 19, 265–277.

    Article  PubMed  CAS  Google Scholar 

  74. Mangoura D. and Dawson G. (1993). Opioid peptides activate phospholipase D and protein kinase C-ɛ in chicken embryo neuron cultures. Proc. Natl. Acad. Sci. USA 90, 2915–2919.

    Article  PubMed  CAS  Google Scholar 

  75. Chen L. and Huang L. Y. (1991). Sustained potentiation of NMDA receptor-mediated glutamate responses through activation of protein kinase C by a mu opioid. Neuron 7, 319–326.

    Article  PubMed  Google Scholar 

  76. Escriba P. V. and Garcia-Sevilla J. A. (1999). Parallel modulation of receptor for activated C kinase 1 and protein kinase C-α and β isoforms in brains of morphine-treated rats. Br. J. Pharmacol. 127, 343–348.

    Article  PubMed  CAS  Google Scholar 

  77. Busquets X., Escriba P. V., Sastre M., and Garcia-Sevilla J. A. (1995). Loss of protein kinase C-α β in brain of heroin addicts and morphine-dependent rats. J. Neurochem. 64, 247–252.

    Article  PubMed  CAS  Google Scholar 

  78. Ventayol P., Busquets X., and Garcia-Sevilla J. A. (1997). Modulation of immunoreactive protein kinase C-α and β isoforms and G proteins by acute and chronic treatments with morphine and other opiate drugs in rat brain. Naunyn-Schmiedeberg’s. Arch. Pharmacol. 355, 491–500.

    Article  CAS  Google Scholar 

  79. Garcia-Sevilla J. A., Ventayol P., Busquets X., La Harpe R., Walzer C., and Guimon J. (1997). Regulation of immunolabelled μ-opioid receptors and protein kinase C-α and ζ isoforms in the frontal cortex of human opiate addicts. Neurosci. Lett. 226, 29–32.

    Article  PubMed  CAS  Google Scholar 

  80. Narita M., Aoki T., Ozaki S., Yajima Y., and Suzuki T. (2001). Involvement of protein kinase Cγ isoform in morphine-induced reinforcing effects. Neuroscience 103, 309–314.

    Article  PubMed  CAS  Google Scholar 

  81. Shahak H., Slotkin T. A., and Yanai J. (2003). Alterations in PKCγ in the mouse hippocampus after prenatal exposure to heroin: a link from cell signaling to behavioral outcome. Dev. Brain. Res. 140, 117–125.

    Article  CAS  Google Scholar 

  82. Choi D. S. and Messing R. O. (2003). Animal models in the study of protein kinase C isozymes. Methods Mol. Biol. 233, 455–473.

    PubMed  CAS  Google Scholar 

  83. Harris R. A., McQuilkin S. J., Paylor R., Abeliovich A., Tonegawa S., and Wehner J. M. (1995). Mutant mice lacking the γ isoform of protein kinase C show decreased behavioral actions of ethanol and altered function of γ-aminobutyrate type A receptors. Proc. Natl. Acad. Sci. USA 92, 3658–3662.

    Article  PubMed  CAS  Google Scholar 

  84. Proctor W. R., Poelchen W., Bowers B. J., Wehner J. M., Messing R. O., and Dunwiddie T. V. (2003). Ethanol differentially enhances hippocampal GABAA receptor-mediated responses in protein kinase Cγ (PKCγ) and PKCɛ null mice. J. Pharmacol. Exp. Ther. 305, 264–270.

    Article  PubMed  CAS  Google Scholar 

  85. Bowers B. J., Owen E. H., Collins A. C., Abeliovich A., Tonegawa S., and Wehner J. M. (1999). Decreased ethanol sensitivity and tolerance development in γ-protein kinase C null mutant mice is dependent on genetic background. Alcohol. Clin. Exp. Res. 23, 387–397.

    PubMed  CAS  Google Scholar 

  86. Bowers B. J., Collins A. C., and Wehner J. M. (2000). Background genotype modulates the effects of γ-PKC on the development of rapid tolerance to ethanol-induced hypothermia. Addict. Biol. 5, 47–58.

    Article  CAS  PubMed  Google Scholar 

  87. Gerlai R. (1996). Gene-targeting studies of mammalian behavior: is it the mutation or the background genotype? Trends Neurosci. 19, 177–181.

    Article  PubMed  CAS  Google Scholar 

  88. Crawley J. N. (2000). What’s Wrong With My Mouse? Behavioral Phenotyping of Transgenic and Knockout Mice. Wiley-Liss, New York.

    Google Scholar 

  89. Schuckit M. A. (1994). Low level of response to alcohol as a predictor of future alcoholism. Am. J. Psychiatry 151, 184–189.

    PubMed  CAS  Google Scholar 

  90. Schuckit M. A. (1994). Alcohol sensitivity and dependence. Exs 71, 341–348.

    PubMed  CAS  Google Scholar 

  91. Kurtz D. L., Stewart R. B., Zweifel M., Li T.-K., and Froehlich J. C. (1996). Genetic differences in tolerance and sensitization to the sedative/hypnotic effects of alcohol. Pharmacol. Biochem. Behav. 53, 585–591.

    Article  PubMed  CAS  Google Scholar 

  92. Thiele T. E., Marsh D. J., Ste. Marie L., Bernstein I. L., and Palmiter R. D. (1998). Ethanol consumption and resistance are inversely related to neuropeptide Y levels. Nature 396, 366–369.

    Article  PubMed  CAS  Google Scholar 

  93. Bowers B. J. and Wehner J. M. (2001). Ethanol consumption and behavioral impulsivity are increased in protein kinase Cγ null mutant mice. J. Neurosci. 21, RC180:1–5.

    Google Scholar 

  94. Bowers B. J., Elliott K. J., and Wehner J. M. (2001). Differential sensitivity to the anxiolytic effects of ethanol and flunitrazepam in PKCγ null mutant mice. Pharmacol. Biochem. Behav. 69, 99–110.

    Article  PubMed  CAS  Google Scholar 

  95. Bowers B. J., Collins A. C., Tritto T., and Wehner J. M. (2000). Mice lacking PKCγ exhibit decreased anxiety. Behav. Genet. 30, 111–121.

    Article  PubMed  CAS  Google Scholar 

  96. Hodge C. W., Mehmert K. K., Kelley S. P., et al. (1999). Supersensitivity to allosteric GABAA receptor modulators and alcohol in mice lacking PKCɛ. Nature Neurosci. 2, 997–1002.

    Article  PubMed  CAS  Google Scholar 

  97. Khasar S. G., Lin Y.-H., Martin A., et al. (1999). A novel nociceptor signaling pathway demonstrated in protein kinase Cɛ mutant mice. Neuron 24, 253–260.

    Article  PubMed  CAS  Google Scholar 

  98. Choi D. S., Wang D., Dadgar J., Chang W. S., and Messing R. O. (2002). Conditional rescue of protein kinase C ɛ regulates ethanol preference and hypnotic sensitivity in adult mice. J. Neurosci. 22, 9905–9911.

    PubMed  CAS  Google Scholar 

  99. Olive M. F., Mehmert K. K., Messing R. O., and Hodge C. W. (2000). Reduced operant ethanol self-administration and in vivo mesolimbic dopamine responses to ethanol in PKCɛ deficient mice. Eur. J. Neurosci. 12, 4131–4140.

    Article  PubMed  CAS  Google Scholar 

  100. Spanagel R. and Hölter S. M. (1999). Long-term alcohol self-administration with repeated alcohol deprivation phases: an animal model of alcoholism? Alcohol Alcohol. 34, 231–243.

    PubMed  CAS  Google Scholar 

  101. Olive M. F., Mehmert K. K., Nannini M. A., Camarini R., Messing R. O., and Hodge C. W. (2001). Reduced ethanol withdrawal severity and altered withdrawal-induced c-fos expression in various brain regions of mice lacking protein kinase Cɛ. Neuroscience 103, 171–179.

    Article  PubMed  CAS  Google Scholar 

  102. Hodge C. W., Raber J., McMahon T., et al. (2002). Decreased anxiety-like behavior, reduced stress hormones, and neurosteroid supersensitivity in mice lacking protein kinase Cɛ. J. Clin. Invest. 110, 1003–1010.

    Article  PubMed  CAS  Google Scholar 

  103. Johnson J. A., Gray M. O., Chen C.-H., and Mochly-Rosen D. (1996). A protein kinase C translocation inhibitor as an isozyme-selective antagonist of cardiac function. J. Biol. Chem. 271, 24,962–24,966.

    CAS  Google Scholar 

  104. Cesare P., Dekker L. V., Sardini A., Parker P. J., and McNaughton P. A. (1999). Specific involvement of PKC-ɛ in sensitization of the neuronal response to painful heat. Neuron 23, 617–624.

    Article  PubMed  CAS  Google Scholar 

  105. Bunting T. A. and Scott BS (1989). Aging and ethanol alter neuronal electric membrane properties. Brain Res. 501, 105–115.

    Article  PubMed  CAS  Google Scholar 

  106. Dina O. A., Barletta J., Chen X., Mutero A., Martin A., Messing R. O., and Levine J. D. (2000). Key role for the epsilon isoform of protein kinase C in painful alcoholic neuropathy in the rat. J. Neurosci. 20, 8614–8619.

    PubMed  CAS  Google Scholar 

  107. Toullec D., Pianetti P., Coste H., et al. (1991). The bisindolylmaleimide GF 109203X is a potent and selective inhibitor of protein kinase C. J. Biol. Chem. 266, 15,771–15,781.

    CAS  Google Scholar 

  108. Li T.-K. (2000). Pharmacogenetics of responses to alcohol and genes that influence alcohol drinking. J. Stud. Alcohol. 61, 5–12.

    PubMed  CAS  Google Scholar 

  109. Begleiter H. and Porjesz B. (1999). What is inherited in the predisposition toward alcoholism? A proposed model. Alcohol. Clin. Exp. Res. 23, 1125–1135.

    Article  PubMed  CAS  Google Scholar 

  110. Schuckit M. A. (1998). Biological, psychological and environmental predictors of the alcoholism risk: a longitudinal study. J. Stud. Alcohol. 59, 485–494.

    PubMed  CAS  Google Scholar 

  111. Raimo E. B. and Schuckit M. A. (1998). Alcohol dependence and mood disorders. Addict. Behav. 23, 933–946.

    Article  PubMed  CAS  Google Scholar 

  112. Schuckit M. A. and Smith T. L. (2000). The relationships of a family history of alcohol dependence, a low level of response to alcohol and six domains of life functioning to the development of alcohol use disorders. J. Stud. Alcohol. 61, 827–835.

    PubMed  CAS  Google Scholar 

  113. Schuckit M. A., Kraft H. S., Hurtado S. L., Tschinkel S. A., Minagawa R., and Shaffer R. A. (2001). A measure of the intensity of response to alcohol in a military population. Am. J. Drug. Alcohol Abuse 27, 749–757.

    Article  PubMed  CAS  Google Scholar 

  114. Li T.-K., Lumeng L., and Doolittle D. P. (1993). Selective breeding for alcohol preference and associated responses. Behav. Genet. 23, 163–170.

    Article  PubMed  CAS  Google Scholar 

  115. Foroud T., Edenberg H. J., Goate A., et al. (2000). Alcoholism susceptibility loci: confirmation studies in a replicate sample and further mapping. Alcohol. Clin. Exp. Res. 24, 933–945.

    Article  PubMed  CAS  Google Scholar 

  116. Wilhelmsen K. C., Schuckit M., Smith T. L., Lee J. V., Segall S. K., Feiler H. S., and Kalmijn J. (2003). The search for genes related to a low-level response to alcohol determined by alcohol challenges. Alcohol. Clin. Exp. Res. 27, 1041–1047.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Ernest Gallo Clinic and Research Center, Department of Neurology, University of California at San Francisco, 94608, Emeryville, CA

    M. Foster Olive & Robert O. Messing

Authors
  1. M. Foster Olive
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert O. Messing
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Foster Olive.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Foster Olive, M., Messing, R.O. Protein kinase C isozymes and addiction. Mol Neurobiol 29, 139–153 (2004). https://doi.org/10.1385/MN:29:2:139

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1385/MN:29:2:139

Index Entries

Search

Navigation