recent publications
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academic article
- Suarez, J., Khom, S., Alen, F., Natividad, L. A., Varodayan, F. P., Patel, R. R., Kirson, D., Arco, R., Ballesta, A., Bajo, M., Rubio, L., Martin-Fardon, R., et al. Cessation of fluoxetine treatment increases alcohol seeking during relapse and dysregulates endocannabinoid and glutamatergic signaling in the central amygdala Addiction Biology 2020 DOI:10.1111/adb.12813 PMID:31339221
- Matzeu, A., Martin-Fardon, R. Targeting the Orexin System for Prescription Opioid Use Disorder Brain Sciences 2020 10 DOI:10.3390/brainsci10040226 PMID:32290110 PMCID:PMC7225970
- Matzen, A., Martin-Fardon, R. Targeting the orexin system for prescription opioid use disorder: Orexin-1 receptor blockade prevents oxycodone taking and seeking in rats Neuropharmacology 2020 164 DOI:10.1016/j.neuropharm.2019.107906 PMID:31841797 PMCID:PMC69544966
- Kim, J. S., Martin-Fardon, R. Possible role of CRF-Hcrt interaction in the infralimbic cortex in the emergence and maintenance of compulsive alcohol-seeking behavior Alcoholism-Clinical and Experimental Research 2020 DOI:10.1111/acer.14264 PMID:31840823
- Matzeu, A., Martin-Fardon, R. Blockade of Orexin Receptors in the Posterior Paraventricular Nucleus of the Thalamus Prevents Stress-Induced Reinstatement of Reward-Seeking Behavior in Rats With a History of Ethanol Dependence Frontiers in Integrative Neuroscience 2020 14 DOI:10.3389/fnint.2020.599710 PMID:33240054 PMCID:PMC7683390
- Pavon, F. J., Polis, I., Stouffer, D. G., Roberto, M., Martin-Fardon, R., de Fonseca, F. R., Parsons, L. H., Serrano, A. COX-2 Inhibition Antagonizes Intra-Accumbens 2-Arachidonoylglycerol-Mediated Reduction in Ethanol Self-Administration in Rats Alcoholism-Clinical and Experimental Research 2020 DOI:10.1111/acer.14456 PMID:32944989
- Pavon, F. J., Serrano, A., Stouffer, D. G., Polis, I., Roberto, M., Cravatt, B. F., Martin-Fardon, R., de Fonseca, F. R., Parsons, L. H. Ethanol-induced alterations in endocannabinoids and relevant neurotransmitters in the nucleus accumbens of fatty acid amide hydrolase knockout mice Addiction Biology 2019 24:1204-1215 DOI:10.1111/adb.12695 PMID:30421483 PMCID:PMC6551299
- Matzeu, A., Terenius, L., Martin-Fardon, R. Exploring sex differences in the attenuation of ethanol drinking by naltrexone in dependent rats during early and protracted abstinence Alcoholism-Clinical and Experimental Research 2018 42:2466-2478 DOI:10.1111/acer.13898 PMID:30320880 PMCID:PMC6286204
- Schmeichel, B. E., Matzeu, A., Koebel, P., Vendruscolo, L. F., Sidhu, H., Shahryari, R., Kieffer, B. L., Koob, G. F., Martin-Fardon, R., Contet, C. Knockdown of hypocretin attenuates extended access of cocaine self-administration in rats Neuropsychopharmacology 2018 43:2373-2382 DOI:10.1038/s41386-018-0054-4 PMID:29703996 PMCID:PMC6180106
- Natividad, L. A., Steinman, M. Q., Laredo, S. A., Irimia, C., Polis, I. Y., Lintz, R., Buczynski, M. W., Martin-Fardon, R., Roberto, M., Parsons, L. H. Phosphorylation of calcium/calmodulin-dependent protein kinase II in the rat dorsal medial prefrontal cortex is associated with alcohol-induced cognitive inflexibility Addiction Biology 2018 23:1117-1129 DOI:10.1111/adb.12568 PMID:28940879 PMCID:PMC5862723
- Gonzalez-Cuevas, G., Martin-Fardon, R., Kerr, T. M., Stouffer, D. G., Parsons, L. H., Hammell, D. C., Banks, S. L., Stinchcomb, A. L., Weiss, F. Unique treatment potential of cannabidiol for the prevention of relapse to drug use: preclinical proof of principle Neuropsychopharmacology 2018 43:2036-2045 DOI:10.1038/s41386-018-0050-8 PMID:29686308 PMCID:PMC6098033
- Matzeu, A., Martin-Fardon, R. Drug seeking and relapse: new evidence of a role for orexin and dynorphin co-transmission in the paraventricular nucleus of the thalamus Frontiers in Neurology 2018 9 DOI:10.3389/fneur.2018.00720
- Serrano, A., Pavon, F. J., Buczynski, M. W., Schlosburg, J., Natividad, L. A., Polis, I. Y., Stouffer, D. G., Zorrilla, E. P., Roberto, M., Cravatt, B. F., Martin-Fardon, R., de Fonseca, F. R., et al. Deficient endocannabinoid signaling in the central amygdala contributes to alcohol dependence-related anxiety-like behavior and excessive alcohol intake Neuropsychopharmacology 2018 43:1840-1850 DOI:10.1038/s41386-018-0055-3 PMID:29748627 PMCID:PMC6046053
- Matzeu, A., Kallupi, M., George, O., Schweitzer, P., Martin-Fardon, R. Dynorphin counteracts orexin in the paraventricular nucleus of the thalamus: cellular and behavioral evidence Neuropsychopharmacology 2018 43:1010-1020 DOI:10.1038/npp.2017.250 PMID:29052613 PMCID:PMC5854806
- Pavon, F. J., Serrano, A., Sidhpura, N., Polis, I., Stouffer, D., de Fonseca, F. R., Cravatt, B. F., Martin-Fardon, R., Parsons, L. H. Fatty acid amide hydrolase (FAAH) inactivation confers enhanced sensitivity to nicotine-induced dopamine release in the mouse nucleus accumbens Addiction Biology 2018 23:723-734 DOI:10.1111/adb.12531 PMID:28660730 PMCID:PMC5747548
- de Guglielmo, G., Matzeu, A., Kononoff, J., Mattioni, J., Martin-Fardon, R., George, O. Cebranopadol blocks the escalation of cocaine intake and conditioned reinstatement of cocaine seeking in rats Journal of Pharmacology and Experimental Therapeutics 2017 362:378-384 DOI:10.1124/jpet.117.241042 PMID:28645915 PMCID:PMC5539589
- Matzeu, A., Kerr, T. M., Weiss, F., Martin-Fardon, R. Orexin-A/hypocretin-1 mediates cocaine-seeking behavior in the posterior paraventricular nucleus of the thalamus via orexin/hypocretin receptor-2 Journal of Pharmacology and Experimental Therapeutics 2016 359:273-279 DOI:10.1124/jpet.116.235945 PMID:27540003 PMCID:PMC5074483
- Martin-Fardon, R., Cauvi, G., Kerr, T. M., Weiss, F. Differential role of hypothalamic orexin/hypocretin neurons in reward seeking motivated by cocaine versus palatable food Addiction Biology 2016 23:6-15 DOI:10.1111/adb.12441 PMID:27558790 PMCID:PMC5325827
- Martin-Fardon, R., Weiss, F. Perseveration of craving: effects of stimuli conditioned to drugs of abuse versus conventional reinforcers differing in demand Addiction Biology 2016 22:923-932 DOI:10.1111/adb.12374 PMID:26864474 PMCID:PMC4980277
- Matzeu, A., Weiss, F., Martin-Fardon, R. Transient inactivation of the posterior paraventricular nucleus of the thalamus blocks cocaine-seeking behavior Neuroscience Letters 2015 608:34-39 DOI:10.1016/j.neulet.2015.10.016 PMID:26455867 PMCID:PMC4639449
- de Guglielmo, G., Martin-Fardon, R., Teshima, K., Ciccocioppo, R., Weiss, F. MT-7716, a potent NOP receptor agonist, preferentially reduces ethanol seeking and reinforcement in post-dependent rats Addiction Biology 2015 20:643-651 DOI:10.1111/adb.12157 PMID:24930632 PMCID:PMC4268094
- Matzeu, A., Cauvi, G., Kerr, T. M., Weiss, F., Martin-Fardon, R. The paraventricular nucleus of the thalamus is differentially recruited by stimuli conditioned to the availability of cocaine versus palatable food Addiction Biology 2015 22:70-77 DOI:10.1111/adb.12280 PMID:26096647 PMCID:PMC4788574
- Martin-Fardon, R., Weiss, F. Blockade of hypocretin receptor-1 preferentially prevents cocaine seeking: comparison with natural reward seeking Neuroreport 2014 25:485-488 DOI:10.1097/wnr.0000000000000120 PMID:24407199 PMCID:PMC3981907
- Matzeu, A., Zamora-Martinez, E. R., Martin-Fardon, R. The paraventricular nucleus of the thalamus is recruited by both natural rewards and drugs of abuse: recent evidence of a pivotal role for orexin/hypocretin signaling in this thalamic nucleus in drug-seeking behavior Frontiers in Behavioral Neuroscience 2014 8:117 DOI:10.3389/fnbeh.2014.00117 PMID:24765071 PMCID:PMC3982054
- Aujla, H., Cannarsa, R., Romualdi, P., Ciccocioppo, R., Martin-Fardon, R., Weiss, F. Modification of anxiety-like behaviors by nociceptin/orphanin FQ (N/OFQ) and time-dependent changes in N/OFQ-NOP gene expression following ethanol withdrawal Addiction Biology 2013 18:467-479 DOI:10.1111/j.1369-1600.2012.00466.x PMID:22804785 PMCID:PMC3477306
- Martin-Fardon, R., Weiss, F. Modeling relapse in animals Current topics in behavioral neurosciences 2013 13:403-32 DOI:10.1007/7854_2012_202 PMID:22389178
- Martin-Fardon, R., Boutrel, B. Orexin/hypocretin (Orx/Hcrt) transmission and drug-seeking behavior: is the paraventricular nucleus of the thalamus (PVT) part of the drug seeking circuitry? Frontiers in Behavioral Neuroscience 2012 6:75 DOI:10.3389/fnbeh.2012.00075 PMID:23162448 PMCID:PMC3494007
- Martin-Fardon, R., Strong, E. M., Weiss, F. Effect of sigma(1) receptor antagonism on ethanol and natural reward seeking Neuroreport 2012 23:809-813 DOI:10.1097/WNR.0b013e32835717c8 PMID:22878224
- Martin-Fardon, R., Weiss, F. (-)-2-oxa-4-aminobicylco[3.1.0]hexane-4,6-dicarboxylic acid (LY379268) and 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]piperidine (MTEP) similarly attenuate stress-induced reinstatement of cocaine seeking Addiction Biology 2012 17:557-564 DOI:10.1111/j.1369-1600.2011.00345.x PMID:21790902 PMCID:PMC3204322
- Martin-Fardon, R., Weiss, F. N-(2-methyl-6-benzoxazolyl)-N'-1,5-naphthyridin-4-yl urea (SB334867), a hypocretin receptor-1 antagonist, preferentially prevents ethanol seeking: comparison with natural reward seeking Addiction Biology 2012 DOI:10.1111/j.1369-1600.2012.00480.x PMID:22830647 PMCID:PMC3491173
- Kufahl, P. R., Martin-Fardon, R., Weiss, F. Enhanced sensitivity to attenuation of conditioned reinstatement by the mGluR 2/3 agonist LY379268 and increased functional activity of mGluR 2/3 in rats with a history of ethanol dependence Neuropsychopharmacology 2011 36:2762-2773 DOI:10.1038/npp.2011.174 PMID:21881571 PMCID:PMC3230501
- Economidou, D., Cippitelli, A., Stopponi, S., Braconi, S., Clementi, S., Ubaldi, M., Martin-Fardon, R., Weiss, F., Massi, M., Ciccocioppo, R. Activation of brain NOP receptors attenuates acute and protracted alcohol withdrawal symptoms in the rat Alcoholism-Clinical and Experimental Research 2011 35:747-755 DOI:10.1111/j.1530-0277.2010.01392.x PMID:21223310 PMCID:PMC3066303
- Hao, Y., Martin-Fardon, R., Weiss, F. Behavioral and functional evidence of metabotropic glutamate receptor 2/3 and metabotropic glutamate receptor 5 dysregulation in cocaine-escalated rats: Factor in the transition to dependence Biological Psychiatry 2010 68:240-248 DOI:10.1016/j.biopsych.2010.02.011 PMID:20416862 PMCID:PMC2907426
- Sidhpura, N., Weiss, F., Martin-Fardon, R. Effects of the mGlu2/3 agonist LY379268 and the mGlu5 antagonist MTEP on ethanol seeking and reinforcement are differentially altered in rats with a history of ethanol dependence Biological Psychiatry 2010 67:804-811 DOI:10.1016/j.biopsych.2010.01.005 PMID:20189165 PMCID:PMC2854322
- Braconi, S., Sidhpura, N., Aujla, H., Martin-Fardon, R., Weiss, F., Ciccocioppo, R. Revisiting intragastric ethanol intubation as a dependence induction method for studies of ethanol reward and motivation in rats Alcoholism-Clinical and Experimental Research 2010 34:538-544 DOI:10.1111/j.1530-0277.2009.01119.x PMID:20028350 PMCID:PMC2858236
- Martin-Fardon, R., Zorrilla, E. P., Ciccocioppo, R., Weiss, F. Role of innate and drug-induced dysregulation of brain stress and arousal systems in addiction: Focus on corticotropin-releasing factor, nociceptin/orphanin FQ, and orexin/hypocretin Brain Research 2010 1314:145-161 DOI:10.1016/j.brainres.2009.12.027 PMID:20026088 PMCID:PMC2819635
- Martin-Fardon, R., Baptista, M. A. S., Dayas, C. V., Weiss, F. Dissociation of the effects of MTEP [3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]piperidine] on conditioned reinstatement and reinforcement: comparison between cocaine and a conventional reinforcer Journal of Pharmacology and Experimental Therapeutics 2009 329:1084-1090 DOI:10.1124/jpet.109.151357 PMID:19258516 PMCID:PMC2683783
- Economidou, D., Hansson, A. C., Weiss, F., Terasmaa, A., Sommer, W. H., Cippitelli, A., Fedeli, A., Martin-Fardon, R., Massi, M., Ciccocioppo, R., Heilig, M. Dysregulation of nociceptin/orphanin FQ activity in the amygdala is linked to excessive alcohol drinking in the rat Biological Psychiatry 2008 64:211-218 DOI:10.1016/j.biopsych.2008.02.004 PMID:18367152 PMCID:PMC4275225
- Aujla, H., Martin-Fardon, R., Weiss, F. Rats with extended access to cocaine exhibit increased stress reactivity and sensitivity to the anxiolytic-like effects of the mGluR 2/3 agonist LY379268 during abstinence Neuropsychopharmacology 2008 33:1818-1826 DOI:10.1038/sj.npp.1301588 PMID:17895914
- Martin-Fardon, R., Ciccocioppo, R., Aujla, H., Weiss, F. The dorsal subiculum mediates the acquisition of conditioned reinstatement of cocaine-seeking Neuropsychopharmacology 2008 33:1827-1834 DOI:10.1038/sj.npp.1301589 PMID:17957218
- Dayas, C. V., McGranahan, T. M., Martin-Fardon, R., Weiss, F. Stimuli linked to ethanol availability activate hypothalamic CART and orexin neurons in a reinstatement model of relapse Biological Psychiatry 2008 63:152-157 DOI:10.1016/j.biopsych.2007.02.002 PMID:17570346
- Gonzalez-Cuevas, G., Aujla, H., Martin-Fardon, R., Lopez-Moreno, J. A., Navarro, M., Weiss, F. Subchronic cannabinoid agonist (WIN 55,212-2) treatment during cocaine abstinence alters subsequent cocaine seeking behavior Neuropsychopharmacology 2007 32:2260-2266 DOI:10.1038/sj.npp.1301365 PMID:17392740
- Martin-Fardon, R., Maurice, T., Aujla, H., Bowen, W. D., Weiss, F. Differential effects of sigma(1) receptor blockade on self-administration and conditioned reinstatement motivated by cocaine vs natural reward Neuropsychopharmacology 2007 32:1967-1973 DOI:10.1038/sj.npp.1301323 PMID:17268407
- Economidou, D., Fedeli, A., Fardon, R. M., Weiss, F., Massi, M., Ciccocioppo, R. Effect of novel nociceptin/orphanin FQ-NOP receptor ligands on ethanol drinking in alcohol-preferring msP rats Peptides 2006 27:3299-3306 DOI:10.1016/j.peptides.2006.09.007 PMID:17097763 PMCID:PMC1847604
- Zhao, Y., Dayas, C. V., Aujla, H., Baptista, M. A. S., Martin-Fardon, R., Weiss, F. Activation of group II metabotropic glutamate receptors attenuates both stress and cue-induced ethanol-seeking and modulates c-fos expression in the hippocampus and amygdala Journal of Neuroscience 2006 26:9967-9974 DOI:10.1523/jneurosci.2384-06.2006 PMID:17005860
- Boutrel, B., Kenny, P. J., Specio, S. E., Martin-Fardon, R., Markou, A., Koob, G. F., de Lecea, L. Role for hypocretin in mediating stress-induced reinstatement of cocaine-seeking behavior Proceedings of the National Academy of Sciences of the United States of America 2005 102:19168-19173 DOI:10.1073/pnas.0507480102 PMID:16357203 PMCID:PMC1323172
- Martin-Fardon, R., Lorentz, C. U., Stuempfig, N. D., Weiss, F. Priming with BTCP, a dopamine reuptake blocker, reinstates cocaine-seeking and enhances cocaine cue-induced reinstatement Pharmacology, Biochemistry and Behavior 2005 82:46-54 DOI:10.1016/j.pbb.2005.07.010 PMID:16099021
- Romieu, P., Meunier, J., Garcia, D., Zozime, N., Martin-Fardon, R., Bowen, W. D., Maurice, T. The sigma(1) (sigma(1)) receptor activation is a key step for the reactivation of cocaine conditioned place preference by drug priming Psychopharmacology 2004 175:154-162 DOI:10.1007/s00213-004-1814-x PMID:14985920
- Baptista, M. A. S., Martin-Fardon, R., Weiss, F. Preferential effects of the metabotropic glutamate 2/3 receptor agonist LY379268 on conditioned reinstatement versus primary reinforcement: comparison between cocaine and a potent conventional reinforcer Journal of Neuroscience 2004 24:4723-4727 DOI:10.1523/jneurosci.0176-04.2004 PMID:15152032
- Dayas, C. V., Martin-Fardon, R., Thorsell, A., Weiss, F. Chronic footshock, but not a physiological stressor, suppresses the alcohol deprivation effect in dependent rats Alcohol and Alcoholism 2004 39:190-196 DOI:10.1093/alcalc/agh046 PMID:15082455
- Ciccocioppo, R., Martin-Fardon, R., Weiss, F. Stimuli associated with a single cocaine experience elicit longlasting cocaine-seeking Nature Neuroscience 2004 7:495-496 DOI:10.1038/nn1219 PMID:15048121
- Martin-Fardon, R., Lorentz, C. U., Kamenka, J. M., Weiss, F. 3-OH-pip-BTCP, a metabolite of the potent DA uptake blocker BTCP, exerts cocaine-like action in rats Neuroreport 2003 14:2439-2444 DOI:10.1097/01.wnr.0000099608.19426.39 PMID:14663207
- Ciccocioppo, R., Lin, D., Martin-Fardon, R., Weiss, F. Reinstatement of ethanol-seeking behavior by drug cues following single versus multiple ethanol intoxication in the rat: Effects of naltrexone Psychopharmacology 2003 168:208-215 DOI:10.1007/s00213-002-1380-z PMID:12664190
- Romieu, P., Martin-Fardon, R., Bowen, W. D., Maurice, T. Sigma(1) receptor-related neuroactive steroids modulate cocaine-induced reward Journal of Neuroscience 2003 23:3572-3576 PMID:12736327
- Izzo, E., Martin-Fardon, R., Koob, G. F., Weiss, F., Sanna, P. P. Neural plasticity and addiction: PI3-kinase and cocaine behavioral sensitization Nature Neuroscience 2002 5:1263-1264 DOI:10.1038/nn977 PMID:12436114
- Ciccocioppo, R., Martin-Fardon, R., Weiss, F. Effect of selective blockade of mu(1) or delta opioid receptors on reinstatement of alcohol-seeking behavior by drug-associated stimuli in rats Neuropsychopharmacology 2002 27:391-399 DOI:10.1016/s0893-133x(02)00302-0 PMID:12225696
- Maurice, T., Martin-Fardon, R., Romieu, P., Matsumoto, R. R. Sigma(1) (sigma(1)) receptor antagonists represent a new strategy against cocaine addiction and toxicity Neuroscience and Biobehavioral Reviews 2002 26:499-527 DOI:10.1016/S0149-7634(02)00017-9 PMID:12204195
- Martin-Fardon, R., Weiss, F. BTCP is a potent reinforcer in rats: comparison of behavior maintained on fixed- and progressive-ratio schedules Pharmacology, Biochemistry and Behavior 2002 72:343-353 DOI:10.1016/s0091-3057(01)00764-x PMID:11900805
- Romieu, P., Phan, V. L., Martin-Fardon, R., Maurice, T. Involvement of the sigma(1) receptor in cocaine-induced conditioned place preference: Possible dependence on dopamine uptake blockade Neuropsychopharmacology 2002 26:444-455 DOI:10.1016/s0893-133x(01)00391-8 PMID:11927169
- Martin-Fardon, R., Kerr, T. M., Deleuze-Masquefa, C., Kamenka, J. M., Weiss, F. Behavioral and neurochemical effects of 3-OH-pip-BTCP, an active metabolite of BTCP in rats Neuroreport 2001 12:4165-4169 DOI:10.1097/00001756-200112210-00060 PMID:11742258
- Weiss, F., Martin-Fardon, R., Ciccocioppo, R., Kerr, T. M., Smith, D. L., Ben-Shahar, O. Enduring resistance to extinction of cocaine-seeking behavior induced by drug-related cues Neuropsychopharmacology 2001 25:361-372 DOI:10.1016/s0893-133x(01)00238-x PMID:11522464
- Ciccocioppo, R., Martin-Fardon, R., Weiss, F., Massi, M. Nociceptin/orphanin FQ inhibits stress- and CRF-induced anorexia in rats Neuroreport 2001 12:1145-1149 DOI:10.1097/00001756-200105080-00019 PMID:11338181
- Romieu, P., Martin-Fardon, R., Maurice, T. Involvement of the sigma(1) receptor in the cocaine-induced conditioned place preference Neuroreport 2000 11:2885-2888 DOI:10.1097/00001756-200009110-00011 PMID:11006959
- Martin-Fardon, R., Weiss, F. N-[1-(2-benzo[b]thiophenyl)Cyclohexyl]- piperidine (BTCP) exerts cocaine-like actions on drug-maintained responding in rats Neuropsychopharmacology 2000 23:316-325 DOI:10.1016/s0893-133x(00)00104-4 PMID:10942855
- Martin-Fardon, R., Ben-Shahar, O., Weiss, F. Non reciprocal cross-sensitization between cocaine and BTCP on locomotor activity in the rat Pharmacology, Biochemistry and Behavior 2000 66:631-635 DOI:10.1016/s0091-3057(00)00262-8 PMID:10899381
- Martin-Fardon, R., Ciccocioppo, R., Massi, M., Weiss, F. Nociceptin prevents stress-induced ethanol- but not cocaine-seeking behavior in rats Neuroreport 2000 11:1939-1943 DOI:10.1097/00001756-200006260-00026 PMID:10884047
- Martin-Fardon, R., Sandillon, F., Thibault, J., Privat, A., Vignon, J. Long-term monitoring of extracellular dopamine concentration in the rat striatum by a repeated microdialysis procedure Journal of Neuroscience Methods 1997 72:123-135 DOI:10.1016/s0165-0270(96)02170-x PMID:9133576
- Martin-Fardon, R., Arnaud, M., Rousseau, E., Kamenka, J. M., Privat, A., Vignon, J. N-[1-(2-Benzo(b)thiophenyl)cyclohexyl]piperidine (BTCP) and cocaine induce similar effects on striatal dopamine: a microdialysis study in freely moving rats Neuroscience Letters 1996 211:179-182 DOI:10.1016/0304-3940(96)12744-0 PMID:8817570
- Coderc, E., Martin-Fardon, R., Vignon, J., Kamenka, J. M. New compounds resulting from structural and biochemical similarities between GBR 1278 and BTCP, two potent inhibitors of dopamine uptake European Journal of Medicinal Chemistry 1993 28:893-898 DOI:10.1016/0223-5234(93)90042-d