Self-Regulation Therapy to Reproduce Drug Effects: A Suggestion Technique to Change Personality and the DRD3 Gene Expression

This study proposes a strategy, based on self-regulation therapy, to change personality and its biological substrate, the DRD3 gene expression. It has been demonstrated that acute doses of stimulating drugs, like methylphenidate, are able to change personality and the expression of certain genes in the short term. On the other hand, self-regulation therapy has been proven to reproduce the effects of drugs. Thus, it is feasible to hope that self-regulation therapy is equally effective as methylphenidate in changing personality and the gene expression. This is a preliminary study with a single-case experimental design with replication in which 2 subjects participated. The results and potential implications for research and psychotherapy are discussed.Amigó Borrás, S.; Caselles Moncho, A.; Micó Ruiz, JC. (2013). Self-Regulation Therapy to Reproduce Drug Effects: A Suggestion Technique to Change Personality and the DRD3 Gene Expression. International Journal of Clinical and Experimental Hypnosis. 61(3):282-304. doi:10.1080/00207144.2013.784094S282304613Accili, D., Fishburn, C. S., Drago, J., Steiner, H., Lachowicz, J. E., Park, B. H., … Fuchs, S. (1996). A targeted mutation of the D3 dopamine receptor gene is associated with hyperactivity in mice. Proceedings of the National Academy of Sciences, 93(5), 1945-1949. doi:10.1073/pnas.93.5.1945Amigó, S., Caselles, A., & Micó, J. C. (2008). A dynamic extraversion model. The brain’s response to a single dose of a stimulant drug. British Journal of Mathematical and Statistical Psychology, 61(1), 211-231. doi:10.1348/000711007x185514Amigó, S., Caselles, A., & Micó, J. C. (2010). General Factor of Personality Questionnaire (GFPQ): Only one Factor to Understand Personality? The Spanish journal of psychology, 13(1), 5-17. doi:10.1017/s1138741600003644Barbanti, P., Bronzetti, E., Ricci, A., Cerbo, R., Fabbrini, G., Buzzi, M. G., … Lenzi, G. L. (1996). Increased density of dopamine D5 receptor in peripheral blood lymphocytes of migraineurs: a marker for migraine? Neuroscience Letters, 207(2), 73-76. doi:10.1016/0304-3940(96)12491-5Barbanti, P., Fabbrini, G., Ricci, A., Bruno, G., Cerbo, R., Bronzetti, E., … Luigi Lenzi, G. (2000). Reduced density of dopamine D2-like receptors on peripheral blood lymphocytes in Alzheimer’s disease. Mechanisms of Ageing and Development, 120(1-3), 65-75. doi:10.1016/s0047-6374(00)00183-4Barbanti, P., Fabbrini, G., Ricci, A., Pascali, M. P., Bronzetti, E., Amenta, F., … Cerbo, R. (2000). Migraine Patients Show an Increased Density of Dopamine D3 and D4 Receptors on Lymphocytes. Cephalalgia, 20(1), 15-19. doi:10.1046/j.1468-2982.2000.00001.xBarr, G. A., Sharpless, N. S., Cooper, S., Schiff, S. R., Paredes, W., & Bridger, W. H. (1983). Classical conditioning, decay and extinction of cocaine-induced hyperactivity and stereotypy. Life Sciences, 33(14), 1341-1351. doi:10.1016/0024-3205(83)90817-2Baumann, F. (1970). Hypnosis and the Adolescent Drug Abuser. American Journal of Clinical Hypnosis, 13(1), 17-21. doi:10.1080/00029157.1970.10402074Bayot, A., Capafons, A., & Cardeña, E. (1997). Emotional Self-Regulation Therapy: A New and Efficacious Treatment for Smoking. American Journal of Clinical Hypnosis, 40(2), 146-156. doi:10.1080/00029157.1997.10403418Berke, J. D., Paletzki, R. F., Aronson, G. J., Hyman, S. E., & Gerfen, C. R. (1998). A Complex Program of Striatal Gene Expression Induced by Dopaminergic Stimulation. The Journal of Neuroscience, 18(14), 5301-5310. doi:10.1523/jneurosci.18-14-05301.1998Blachly, P. H. (1971). An «Electric Needle» for Aversive Conditioning of the Needle Ritual. International Journal of the Addictions, 6(2), 327-328. doi:10.3109/10826087109057791Brown, E., Robertson, G., & Fibiger, H. (1992). Evidence for conditional neuronal activation following exposure to a cocaine-paired environment: role of forebrain limbic structures. The Journal of Neuroscience, 12(10), 4112-4121. doi:10.1523/jneurosci.12-10-04112.1992Caine, S., & Koob, G. (1993). Modulation of cocaine self-administration in the rat through D-3 dopamine receptors. Science, 260(5115), 1814-1816. doi:10.1126/science.8099761Capafons, A., & Amigoó, S. (1995). Emotional Self-Regulation Therapy for Smoking Reduction: Description and Initial Empirical Data. International Journal of Clinical and Experimental Hypnosis, 43(1), 7-19. doi:10.1080/00207149508409372Caselles, A., Micó, J. C., & Amigó, S. (2010). Cocaine addiction and personality: A mathematical model. British Journal of Mathematical and Statistical Psychology, 63(2), 449-480. doi:10.1348/000711009x470768Caselles, A., Micó, J. C., & Amigó, S. (2011). Dynamics of the General Factor of Personality in Response to a Single Dose of Caffeine. The Spanish journal of psychology, 14(2), 675-692. doi:10.5209/rev_sjop.2011.v14.n2.16Comings, D., Gade-Andavolu, R., Gonzalez, N., Wu, S., Muhleman, D., Blake, H., … MacMurray, J. (2001). A multivariate analysis of 59 candidate genes in personality traits: the temperament and character inventory. Clinical Genetics, 58(5), 375-385. doi:10.1034/j.1399-0004.2000.580508.xCzermak, C., Lehofer, M., Renger, H., Wagner, E. M., Lemonis, L., Rohrhofer, A., … Liebmann, P. M. (2004). Dopamine receptor D3 mRNA expression in human lymphocytes is negatively correlated with the personality trait of persistence. Journal of Neuroimmunology, 150(1-2), 145-149. doi:10.1016/j.jneuroim.2004.01.009Daly, S. A., & Waddington, J. L. (1993). Behavioural effects of the putative D-3 dopamine receptor agonist 7-OH-DPAT in relation to other «D-2-like» agonists. Neuropharmacology, 32(5), 509-510. doi:10.1016/0028-3908(93)90177-5Gilbert, D. G., & Hagen, R. L. (1985). Electrodermal responses to movie stressors: Nicotine × extraversion interactions. Personality and Individual Differences, 6(5), 573-578. doi:10.1016/0191-8869(85)90006-6Gilbert, D. B., Millar, J., & Cooper, S. J. (1995). The putative dopamine D3 agonist, 7-OH-DPAT, reduces dopamine release in the nucleus accumbens and electrical self-stimulation to the ventral tegmentum. Brain Research, 681(1-2), 1-7. doi:10.1016/0006-8993(95)00247-nHastings, A. (2006). An Extended Nondrug MDMA-Like Experience Evoked Through Posthypnotic Suggestion. Journal of Psychoactive Drugs, 38(3), 273-283. doi:10.1080/02791072.2006.10399853Ilani, T., Ben-Shachar, D., Strous, R. D., Mazor, M., Sheinkman, A., Kotler, M., & Fuchs, S. (2001). A peripheral marker for schizophrenia: Increased levels of D3 dopamine receptor mRNA in blood lymphocytes. Proceedings of the National Academy of Sciences, 98(2), 625-628. doi:10.1073/pnas.98.2.625Kollins, S. H., MacDonald, E. K., & Rush, C. R. (2001). Assessing the abuse potential of methylphenidate in nonhuman and human subjects: a review. Pharmacology Biochemistry and Behavior, 68(3), 611-627. doi:10.1016/s0091-3057(01)00464-6Lejeune, F., & Millan, M. J. (1995). Activation of dopamine D3 autoreceptors inhibits firing of ventral tegmental dopaminergic neurones in vivo. European Journal of Pharmacology, 275(3), R7-R9. doi:10.1016/0014-2999(95)00106-uLevant, B. (1998). Differential distribution of D3 dopamine receptors in the brains of several mammalian species. Brain Research, 800(2), 269-274. doi:10.1016/s0006-8993(98)00529-0LEVINE, D. G. (1974). «Needle Freaks»: Compulsive Self-Injection Drug Users. American Journal of Psychiatry, 131(3), 297-300. doi:10.1176/ajp.131.3.297LYNCH, J. J., STEIN, E. A., & FERTZIGER, A. P. (1976). AN ANALYSIS OF 70 YEARS OF MORPHINE CLASSICAL CONDITIONING. The Journal of Nervous and Mental Disease, 163(1), 47-58. doi:10.1097/00005053-197607000-00007Merchant, K. M., Figur, L. M., & Evans, D. L. (1996). Induction of c-fos mRNA in Rat Medial Prefrontal Cortex by Antipsychotic Drugs: Role of Dopamine D2 and D3 Receptors. Cerebral Cortex, 6(4), 561-570. doi:10.1093/cercor/6.4.561Muntaner, C., Cascella, N. G., Kumor, K. M., Nagoshi, C., Herning, R., & Jaffe, J. (1989). Placebo responses to cocaine administration in humans: effects of prior administrations and verbal instructions. Psychopharmacology, 99(2), 282-286. doi:10.1007/bf00442823Musek, J. (2007). A general factor of personality: Evidence for the Big One in the five-factor model. Journal of Research in Personality, 41(6), 1213-1233. doi:10.1016/j.jrp.2007.02.003Nagai, Y., Ueno, S., Saeki, Y., Soga, F., Hirano, M., & Yanagihara, T. (1996). Decrease of the D3 dopamine receptor mRNA expression in lymphocytes from patients with Parkinson’s disease. Neurology, 46(3), 791-795. doi:10.1212/wnl.46.3.791Neisewander, J. L., Baker, D. A., Fuchs, R. A., Tran-Nguyen, L. T. L., Palmer, A., & Marshall, J. F. (2000). Fos Protein Expression and Cocaine-Seeking Behavior in Rats after Exposure to a Cocaine Self-Administration Environment. The Journal of Neuroscience, 20(2), 798-805. doi:10.1523/jneurosci.20-02-00798.2000IMissbrandt, H., Ekman, A., Eriksson, E., & Heilig, M. (1995). Dopamine D3 receptor antisense influences dopamine synthesis in rat brain. NeuroReport, 6(3), 573-576. doi:10.1097/00001756-199502000-00041O’BRIEN, C. P., CHILDRESS, A. R., McLELLAN, A. T., & EHRMAN, R. (1992). Classical Conditioning in Drug-Dependent Humans. Annals of the New York Academy of Sciences, 654(1 The Neurobiol), 400-415. doi:10.1111/j.1749-6632.1992.tb25984.xO’Brien, C. P., Nace, E. P., Mintz, J., Meyers, A. L., & Ream, N. (1980). Follow-up of Vietnam veterans. I. relapse to drug use after Vietnam service. Drug and Alcohol Dependence, 5(5), 333-340. doi:10.1016/0376-8716(80)90159-3Pilla, M., Perachon, S., Sautel, F., Garrido, F., Mann, A., Wermuth, C. G., … Sokoloff, P. (1999). Selective inhibition of cocaine-seeking behaviour by a partial dopamine D3 receptor agonist. Nature, 400(6742), 371-375. doi:10.1038/22560Post, R. M., Lockfeld, A., Squillace, K. M., & Contel, N. R. (1981). Drug-environment interaction: Context dependency of cocaine-induced behavioral sensitization. Life Sciences, 28(7), 755-760. doi:10.1016/0024-3205(81)90157-0Ricci, A., Bronzetti, E., Mignini, F., Tayebati, S. K., Zaccheo, D., & Amenta, F. (1999). Dopamine D1-like receptor subtypes in human peripheral blood lymphocytes. Journal of Neuroimmunology, 96(2), 234-240. doi:10.1016/s0165-5728(99)00042-9Schiltz, C. A., Kelley, A. E., & Landry, C. F. (2005). Contextual cues associated with nicotine administration increasearcmRNA expression in corticolimbic areas of the rat brain. European Journal of Neuroscience, 21(6), 1703-1711. doi:10.1111/j.1460-9568.2005.04001.xSchutte, N. S., Malouff, J. M., Segrera, E., Wolf, A., & Rodgers, L. (2003). States reflecting the Big Five dimensions. Personality and Individual Differences, 34(4), 591-603. doi:10.1016/s0191-8869(02)00031-4Smith, B. D., Rockwell-Tischer, S., & Davidson, R. (1986). Extraversion and arousal: Effects of attentional conditions on electrodermal activity. Personality and Individual Differences, 7(3), 293-303. doi:10.1016/0191-8869(86)90004-8Stewart, J., de Wit, H., & Eikelboom, R. (1984). Role of unconditioned and conditioned drug effects in the self-administration of opiates and stimulants. Psychological Review, 91(2), 251-268. doi:10.1037/0033-295x.91.2.251Strange, P. G. (1993). New insights into dopamine receptors in the central nervous system. Neurochemistry International, 22(3), 223-236. doi:10.1016/0197-0186(93)90050-fSuzuki, M., Hurd, Y. L., Sokoloff, P., Schwartz, J.-C., & Sedvall, G. (1998). D3 dopamine receptor mRNA is widely expressed in the human brain. Brain Research, 779(1-2), 58-74. doi:10.1016/s0006-8993(97)01078-0Takahashi, N., Nagai, Y., Ueno, S., Saeki, Y., & Yanagihara, T. (1992). Human peripheral blood lymphocytes express D5 dopamine receptor gene and transcribe the two pseudogenes. FEBS Letters, 314(1), 23-25. doi:10.1016/0014-5793(92)81452-rTorres, G., & Rivier, C. (1994). Induction of c-fos in rat brain by acute cocaine and fenfluramine exposure: a comparison study. Brain Research, 647(1), 1-9. doi:10.1016/0006-8993(94)91391-9Volkow, N. D., Wang, G.-J., Fowler, J. S., Gatley, S. J., Logan, J., Ding, Y.-S., … Pappas, N. (1998). Dopamine Transporter Occupancies in the Human Brain Induced by Therapeutic Doses of Oral Methylphenidate. American Journal of Psychiatry, 155(10), 1325-1331. doi:10.1176/ajp.155.10.1325Volkow, N. D., Wang, G.-J., Fowler, J. S., Telang, F., Maynard, L., Logan, J., … Swanson, J. M. (2004). Evidence That Methylphenidate Enhances the Saliency of a Mathematical Task by Increasing Dopamine in the Human Brain. American Journal of Psychiatry, 161(7), 1173-1180. doi:10.1176/appi.ajp.161.7.1173Vorel, S. R., Ashby, C. R., Paul, M., Liu, X., Hayes, R., Hagan, J. J., … Gardner, E. L. (2002). Dopamine D3Receptor Antagonism Inhibits Cocaine-Seeking and Cocaine-Enhanced Brain Reward in Rats. The Journal of Neuroscience, 22(21), 9595-9603. doi:10.1523/jneurosci.22-21-09595.2002Yano, M., & Steiner, H. (2004). Topography of Methylphenidate (Ritalin)-Induced Gene Regulation in the Striatum: Differential Effects on c-Fos, Substance P and Opioid Peptides. Neuropsychopharmacology, 30(5), 901-915. doi:10.1038/sj.npp.130061

Comparative Analyses of SUV420H1 Isoforms and SUV420H2 Reveal Differences in Their Cellular Localization and Effects on Myogenic Differentiation

Methylation of histone H4 on lysine 20 plays critical roles in chromatin structure and function via mono- (H4K20me1), di- (H4K20me2), and trimethyl (H4K20me3) derivatives. In previous analyses of histone methylation dynamics in mid-gestation mouse embryos, we documented marked changes in H4K20 methylation during cell differentiation. These changes were particularly robust during myogenesis, both in vivo and in cell culture, where we observed a transition from H4K20me1 to H4K20me3. To assess the significance of this change, we used a gain-of-function strategy involving the lysine methyltransferases SUV420H1 and SUV420H2, which catalyze H4K20me2 and H4K20me3. At the same time, we characterized a second isoform of SUV420H1 (designated SUV420H1_i2) and compared the activity of all three SUV420H proteins with regard to localization and H4K20 methylation.Immunofluorescence revealed that exogenous SUV420H1_i2 was distributed throughout the cell, while a substantial portion of SUV420H1_i1 and SUV420H2 displayed the expected association with constitutive heterochromatin. Moreover, SUV420H1_i2 distribution was unaffected by co-expression of heterochromatin protein-1α, which increased the targeting of SUV420H1_i1 and SUV420H2 to regions of pericentromeric heterochromatin. Consistent with their distributions, SUV420H1_i2 caused an increase in H4K20me3 levels throughout the nucleus, whereas SUV420H1_i1 and SUV420H2 facilitated an increase in pericentric H4K20me3. Striking differences continued when the SUV420H proteins were tested in the C2C12 myogenic model system. Specifically, although SUV420H1_i2 induced precocious appearance of the differentiation marker Myogenin in the presence of mitogens, only SUV420H2 maintained a Myogenin-enriched population over the course of differentiation. Paradoxically, SUV420H1_i1 could not be expressed in C2C12 cells, which suggests it is under post-transcriptional or post-translational control.These data indicate that SUV420H proteins differ substantially in their localization and activity. Importantly, SUV420H2 can induce a transition from H4K20me1 to H4K20me3 in regions of constitutive heterochromatin that is sufficient to enhance myogenic differentiation, suggesting it can act an as epigenetic ‘switch’ in this process

G (2000) Molecular manipulation of G-protein-coupled receptors: A new avenue into drug discovery. Curr Med Chem 7(9): 889–896

Abstract: During the past 10 years or so, associated with the introduction of molecular biology techniques to G protein-coupled receptor (GPCR) research, outstanding progress has been made in understanding the mechanisms of action of these key proteins and their physiological functions. in-vivo manipulation of levels of GPCRs using transgenic and gene knock-out approaches have been particularly successful in assessing the roles of specific GPCRs in animal physiology. Drug discovery is aiming to produce highly specific compounds based on subtle definition of receptor subtypes which can best be studied using heterologous expression of wild type or mutated forms of cDNA or genes encoding these proteins. Furthermore, new therapeutic opportunities may be provided by investigation of orphan receptors, the natural ligands for which remain unidentified. Some human diseases have been shown to be associated with rare mutations of GPCRs and the possibility that widely distributed polymorphisms in GPCR genes may allow selective therapeutic strategies for population subgroups is driving the development of the science of pharmacogenetics

Toxoplasma gondii gene expression is under the control of regulatory pathways acting through chromatin structure.

International audienceThe activity state of a gene is determined by a complex regulatory network of co-acting factors affecting the structure of the chromatin into which the gene is embedded. While significant changes of the transcriptome occur during cell differentiation in apicomplexan parasites, basic mechanisms controlling gene expression are still unknown. Recent studies support and expand the concept of the chromatin environment being key factor for the control of transcriptional activity in these lower eukaryotes organisms. Here, we review recent advances in the field of epigenetic gene regulation in Toxoplasma gondii, the model apicomplexan

Tribological behavior of thin electroplated and chemically deposited Ni-P coatings on copper substrates

International audienceThe paper deals with the study of the tribological behavior of thin (1 and 5 μm thick) Ni-P coatings formed on plates made of electrotechnical copper by electroplating and chemical deposition. It has been found that after heat treatment, owing to diffusion processes, the coating components are capable of penetrating into the substrate material—to a depth of 15 μm for electroplated coatings and of 35 μm for chemically deposited coatings)—and influencing the mechanical properties of a specimen such as the hardness and friction coefficient. A correlation between the wear mode of the coating and the method of its deposition has been found. The results show that thin (one μm thick and lesser) Ni-P chemically deposited coatings are promising for being used in friction units of precise mechanical devices