Genetics of Benzodiazepines, Barbiturates, and Anesthetics

  • Edward J. Gallaher
  • John C. CrabbeJr.

Abstract

The behavioral effects of the benzodiazepines (BZs) first attracted attention when chlordiazepoxide was observed to produce a taming effect in previously vicious monkeys. Clinical trials soon followed, and chlordiazepoxide (Librium®) was introduced into clinical practice in 1960, followed closely by diazepam (Valium®) in 1963. Primarily because of their extraordinary safety, these drugs rapidly replaced the barbiturates as anxiolytics of choice. The benzodiazepines soon became the most widely prescribed psychoactive drugs, arid indeed the most-prescribed drugs of any class, until attention was directed to their overuse and potential dependence liability. They continue to be used widely for their sedative-hypnotic, anxiolytic, anticonvulsant, and muscle relaxant effects, and despite the abovementioned dependence liability, they remain among the most useful and safest drugs available.

Keywords

Caffeine Chlordiazepoxide Pentobarbital Sawdust Thiopental 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Alda, M., Duorakova, M., Posmurova, M., Malikova, M., Zvolsky, P., and Filip, V., 1987, Pharmacogenetic study with diazepam in twins, Neuropsychobiology 17:4–8.PubMedCrossRefGoogle Scholar
  2. Alho, H., Miyata, M., Korpi, E., Kiianmaa, K., and Guidotti, A., 1987, Studies of a brain polypeptide functioning as a putative endogenous ligand to benzodiazepine recognition sites in rats selectively bred for alcohol related behavior, Alcohol Alcoholism 1:637–641.Google Scholar
  3. Allan, A. M., Gallaher, E. J., Gionet, S. E., and Harris, R. A., 1988, Genetic selection for benzodiazepine ataxia produces functional changes in the γ-aminobutyric acid receptor chloride channel complex, Brain Res. 452:118–126.PubMedCrossRefGoogle Scholar
  4. Belknap, J. K., 1991, Where are the mu-opioid receptors that mediate analgesia? An autoradio-graphic study in the HAR and LAR selected lines, J. Addict. Dis. 10:29–44 (1991).PubMedCrossRefGoogle Scholar
  5. Belknap, J. K., and Mitchell, M. A., 1981, Barbiturate dependence in mice; effects on body temperature regulation, J. Pharmacol. Exp. Ther. 218:647–652.PubMedGoogle Scholar
  6. Belknap, J. K., Waddingham, S., and Ondrusek, G., 1973, Barbiturate dependence in mice induced by a short-term oral procedure, Physiol. Psychol. 1:394–396.Google Scholar
  7. Belknap, J. K., Ondrusek, J. G., Berg, J., and Waddingham, S., 1977, Barbiturate dependence in mice: Effects of continuous vs. discontinuous drug administration, Psychopharmacology 51:195–198.PubMedCrossRefGoogle Scholar
  8. Belknap, J. K., Crabbe, J. C., and Laursen, S. E., 1989, Ethanol and diazepam withdrawal convulsions are extensively codetermined in WSP and WSR mice, Life Sci. 44:2075–2080.PubMedCrossRefGoogle Scholar
  9. Bertilsson, L., Henthorn, T. K., Sanz, E., Tybring, G., Sawe, J., and Villen, T., 1989, Importance of genetic factors in the regulation of diazepam metabolism: Relationship to S-mephenytoin, but not debrisoquin, hydroxylation phenotype, Clin. Pharmacol. Ther. 45:348–355.PubMedCrossRefGoogle Scholar
  10. Biscoe, T. J., and Fry, J. P., 1982, Some pharmacological studies on the spastic mouse, Br. J. Pharmacol. 75:23–35.PubMedCrossRefGoogle Scholar
  11. Booker, J. G., Dailey, J. W., Jobe, P. C., and Lane, J. D., 1986, Cerebral cortical GABA and benzodiazepine binding sites in genetically seizure prone rats, Life Sci. 39:799–806.PubMedCrossRefGoogle Scholar
  12. Bowers, B. J., and Wehner, J. M., 1989, Interaction of ethanol and stress with the GABA/BZ receptor in LS and SS mice, Brain Res. Bull. 23:53–59.PubMedCrossRefGoogle Scholar
  13. Brailowsky, S., Silva-Barrat, C., Menini, C., Riche, D., and R. Naquet, 1989, Effects of localized, chronic GABA infusions into different cortical areas of the photosensitive baboon, Papio papio, Electroencephalogr. Clin. Neurophysiol. 72:147–156.CrossRefGoogle Scholar
  14. Builione, R. S., 1988, The behavioral and genetic determinants of anxiety as measured by the effects of anti-anxiety agents in mice, Ph.D. thesis, City University of New York.Google Scholar
  15. Caboche, J., Mitrovic, N., Le, S. F., Besson, M. J., Sauter, A., and Maurin, Y., 1989, Postnatal evolution of the γ-aminobutyric acid/benzodiazepine receptor complex in a model of inherited epilepsy: The quaking mouse, J. Neurochem. 52:419–427.PubMedCrossRefGoogle Scholar
  16. Chai, E., Roberts, E., and Sidman, R. L., 1962, Influence of aminoxyacetic acid, a γ-aminobutyrate transaminase inhibitor, on hereditary spastic defect in the mouse, Proc. Soc. Exp. Biol Med. 109:491–495.PubMedCrossRefGoogle Scholar
  17. Chan, A. W. K., and Siemens, A. J., 1979, Development of acute tolerance to pentobarbital: Differential effects in mice, Biochem. Pharmacol. 28:549–552.PubMedCrossRefGoogle Scholar
  18. Crawley, J. N., and Davis, L. G., 1982, Baseline exploratory activity predicts anxiolytic responsiveness to diazepam in five mouse strains, Brain Res. Bull. 8:609–612.PubMedCrossRefGoogle Scholar
  19. Depaulis, A., Vergnes, M., Marescaux, C., Lannes, B., and Warter, J. M., 1988, Evidence that activation of GABA receptors in the substantia nigra suppresses spontaneous spike-and-wave discharges in the rat, Brain Res. 448:20–29.PubMedCrossRefGoogle Scholar
  20. DesForges, C., Venault, P., Dodd, R. H., Chapouthier, G., and Roubertoux, P. L., 1989, Beta-carboline-induced seizures in mice: Genetic analysis., Pharmacol. Biochem. Behav. 34:733–737.PubMedCrossRefGoogle Scholar
  21. Engel, J., and Liljequist, S., 1983, The involvement of different central neurotransmitters in mediating the stimulatory and sedative effects of ethanol, in: Stress and Alcohol use (L. Pohorecky and J. Brick, eds.), Elsevier, New York, pp. 154–169.Google Scholar
  22. Faingold, C. L., 1988, The genetically epilepsy-prone rat, Gen. Pharmacol. 19:331–338.PubMedCrossRefGoogle Scholar
  23. Faingold, C. L., Gehlbach, G., and Caspary, D. M., 1986, Decreased effectiveness of GABA-mediated inhibition in the inferior colliculus of the genetically epilepsy-prone rat, Exp Neurol. 93:145–159.PubMedCrossRefGoogle Scholar
  24. File, S. E., 1983, Strain differences in mice in the development of tolerance to the antipentyle-netetrazol effects of diazepam, Neurosci. Lett. 42:95–98.PubMedCrossRefGoogle Scholar
  25. File, S. E., Greenblatt, D. J., Martin, I. L., and Brown, C., 1985, Long-lasting anticonvulsant effects of diazepam in different mouse strains: Correlations with brain concentrations and receptor occupancy, Psychopharmacology 86:137–141.PubMedCrossRefGoogle Scholar
  26. Fisher, T. E., Johnson, D. D., Tuchek, J. M., and Crawford, R. D., 1985, Evidence for the pharmacological relevance of benzodiazepine receptors to anticonvulsant activity, Physiol. Pharmacol. 63:1477–1479.CrossRefGoogle Scholar
  27. Gallaher, E. J., and Gionet, S. E., 1988a, Initial sensitivity and tolerance to ethanol in mice genetically selected for diazepam sensitivity, Alcoholism Clin. Exp. Res. 12:77–80.CrossRefGoogle Scholar
  28. Gallaher, E. J., and Gionet, S. E., 1988b, Seizure thresholds in diazepam-sensitive and-resistant mice, Soc. Neurosci. Abstr. 14:350.Google Scholar
  29. Gallaher, E. J., and Gionet, S. E., 1989, Effect of GABA-benzodiazepine receptor ligands on seizure threshold in diazepam-sensitive and-resistant mice, Soc. Neurosci. Abstr. 15:668.Google Scholar
  30. Gallaher, E. J., Gionet, S. E., and Hollister, L. E., 1986, The effect of various sedative hypnotics on mice selectively bred for diazepam sensitivity, Pharmacologist 28:129.Google Scholar
  31. Gallaher, E. J., Hollister, L. E., Gionet, S. E., and Crabbe, J. C., 1987, Mouse lines selected for genetic differences in diazepam sensitivity, Psychopharmacology (Berl.). 93:25–30.PubMedCrossRefGoogle Scholar
  32. Gallaher, E. J., Gionet, S. E., and Feller, D. M., 1991, Behavioral and neurochemical studies in diazepam-sensitive and-resistant mice, J. Addict. Dis. 10:45–60(1991).PubMedCrossRefGoogle Scholar
  33. Gentsch, C., Lichtsteiner, M., and Feer, H., 1988, Genetic and environmental influences on behavioral and neurochemical aspects of emotionality in rats, Experientia 44:482–490.PubMedCrossRefGoogle Scholar
  34. Hall, R. C. W., and Zisook, S., 1981, Paradoxical reactions to benzodiazepines, Br. J. Clin. Pharmacol. 11:99S–104S.PubMedCrossRefGoogle Scholar
  35. Harris, R. A., and Allan, A. M., 1985, Functional coupling of GABA receptors to chloride channels in brain membranes, Science 228:1108–1110.PubMedCrossRefGoogle Scholar
  36. Hebebrand, J., and Friedl, W., 1987, Phylogenetic receptor research: Implications in studying psychiatric and neurological disease, J. Psychiatr. Res. 21:531–537.PubMedCrossRefGoogle Scholar
  37. Hebebrand, J., Friedl, W., Unverzagt, B., and Propping, P., 1986, Benzodiazepine receptor subunits in avian brain, J. Neurochem. 47:790–793.PubMedCrossRefGoogle Scholar
  38. Heller, A. H., and Hallet, M., 1982, Elecrophysiological studies with the spastic mutant mouse, Brain Res. 234:299–308.PubMedCrossRefGoogle Scholar
  39. Inayama, M., Suzuki, T., Misawa, M., and Meisch, R. A., 1990, Diazepam oral self-administration in Lewis and Fischer 344 inbred rat strains, Eur. J. Pharmacol. 183:1983.CrossRefGoogle Scholar
  40. Jensen, L. H., Marescaux, C., Vergnes, M., Micheletti, G., and Petersen, E. N., 1984, Antiepileptic action of the beta-carboline ZK 91296 in a genetic petit mal model in rats, Eur. J. Pharmacol. 102:521–524.PubMedCrossRefGoogle Scholar
  41. Koblin, D. D., Dong, D. E., Deady, J. E., and Eger, E. I., 1980, Selective breeding alters murine resistance to nitrous oxide without alteration in synaptic membrane lipid composition, Anesthesiology 52:401–407.PubMedCrossRefGoogle Scholar
  42. Koblin, D. D., Deady, J. E., and Eger, E. I., 1982a, Potencies of inhaled anesthetics and alcohol in mice selectively bred for resistance and susceptibility to nitrous oxide anesthesia, Anesthesiology 56:18–24.PubMedCrossRefGoogle Scholar
  43. Koblin, D. D., O’Connor, B., Deady, J., and Eger, E. I., 1982b, Potencies of convulsant drugs in mice selectively bred for resistance and susceptibility to nitrous oxide anesthesia, Anesthesiology 56:25–28.PubMedCrossRefGoogle Scholar
  44. Koblin, D. D., Lurz, F. W., O’Connor, B., Nelson, N. T., Eger, E. I., and Bainton, C. R., 1984, Potencies of barbiturates in mice selectively bred for resistance of susceptibility to nitrous oxide anesthesia, Anesth. Analg. 63:35–39.PubMedCrossRefGoogle Scholar
  45. Korpi, E. R., and Uusi, O. M., 1989, GABAA receptor-mediated chloride flux in brain homogenates from rat lines with differing innate alcohol sensitivities, Neuroscience 32:387–392.PubMedCrossRefGoogle Scholar
  46. Kosobud, A., and Crabbe, J. C., 1990, Genetic correlations among inbred strain sensitivities to convulsions induced by nine convulsant drugs, Brain Res. 526:8–16.PubMedCrossRefGoogle Scholar
  47. Lane, P. W., Ganser, A. L., Kerner, A.-L., and White, W. F., 1987, Spasmodic, a mutation on chromosome 11 in the mouse, J. Hered. 78:353–356.PubMedGoogle Scholar
  48. Little, H. J., Nutt, D. J., and Taylor, S. C., 1984, Acute and chronic effects of the benzodiazepine receptor ligand FG-7142, Psychopharmacology 94:435–436.Google Scholar
  49. Lloyd, K. G., Munari, C., Worms, P., Bossi, L., and Morselli, P. L., 1983, Indications for the use of gg-aminobutyric acid (GABA)-agonists in convulsant disorders, Prog. Clin. Biol. Res. 124:285–297.PubMedGoogle Scholar
  50. Lolait, S. J., O’Carroll, A. M., Kusano, K., Muller, J. M., Brownstein, M. J., and Mahan, L. C., 1989, Cloning and expression of a novel rat GABAA receptor, FEBS Lett. 246:145–148.PubMedCrossRefGoogle Scholar
  51. Loscher, W., 1985, Anticonvulsant action in the epileptic gerbil of novel inhibitors of GABA uptake, Eur. J. Pharmacol. 110:103–108.PubMedCrossRefGoogle Scholar
  52. Loscher, W., 1986, Development of tolerance to the anticonvulsant effect of GABAmimetic drugs in genetically epilepsy-prone gerbils, Pharmacol. Biochem. Behav. 24:1007–1013.PubMedCrossRefGoogle Scholar
  53. Malminen, O., and Korpi, E. R., 1988, GABA/benzodiazepine receptor/chloride ionophore complex in brains of rat lines selectively bred for differences in ethanol-induced motor impairment, Alcohol 5:239–249.PubMedCrossRefGoogle Scholar
  54. Marley, R. J., and Wehner, J. M., 1987, Correlation between the enhancement of flunitrazepam binding by GABA and seizure susceptibility in mice, Life Sci. 40:2215–2224.PubMedCrossRefGoogle Scholar
  55. Marley, R. J., Gaffney, D., and Wehner, J. M., 1986, Genetic influences on GABA-related seizures, Pharmacol Biochem Behav. 24:665–672.PubMedCrossRefGoogle Scholar
  56. Marley, R. J., Stinchcomb, A., and Wehner, J. M., 1988, Further characterization of benzodiazepine receptor differences in long-sleep and short-sleep mice, Life Sci. 43:1223–1231.PubMedCrossRefGoogle Scholar
  57. Martin, I. L., 1987, The benzodiazepines and their receptors: 25 years of progress, Neuropharmacology 26:957–970.PubMedCrossRefGoogle Scholar
  58. McIntyre, T. D., and Alpern, H. P., 1986, Thiopental, phenobarbital, and chlordiazepoxide induce the same differences in narcotic reaction as ethanol in long-sleep and short-sleep selectively-bred mice, Pharmacol. Biochem. Behav. 24:895–898.PubMedCrossRefGoogle Scholar
  59. Mclntyre, T. D., and Alpern, H. P., 1989, Patterns of convulsive susceptibility in the long-sleep and short-sleep selected mouse lines, Brain Res. Bull. 22:859–865.CrossRefGoogle Scholar
  60. Meldrum, B. S., 1989, GABAergic mechanisms in the pathogenesis and treatment of epilepsy, Br. J. Clin. Pharmacol. 1:3S–11S.CrossRefGoogle Scholar
  61. Mohler, H., and Okada, T., 1977, Benzodiazepine receptor: Demonstration in the central nervous system, Science 198:849–851.PubMedCrossRefGoogle Scholar
  62. Muller, W. F., 1987, The Scientific Basis of Psychiatry, Volume 3, The Benzodiazepine Receptor, Cambridge University Press, New York.Google Scholar
  63. Nabeshima, T., and Ho, I. K., 1981, Pharmacological responses to pentobarbital in different strains of mice, J. Pharmacol. Exp. Ther. 216:198–204.PubMedGoogle Scholar
  64. Nielsen, M., Braestrup, C., and Squires, R. F., 1978, Evidence for a late evolutionary appearance of brain-specific benzodiazepine receptors: An investigation of 18 vertebrate and 5 invertebrate species, Brain Res. 141:342–346.PubMedCrossRefGoogle Scholar
  65. Nutt, D. J., and Lister, R. G., 1988, Strain differences in response to a benzodiazepine receptor inverse agonist (FG 7142) in mice, Psychopharmacology 94:435–436.CrossRefGoogle Scholar
  66. Olsen, R. W., and Tobin, A. J., 1990, Molecular biology of GABA-A receptors, FASEB J. 4:1469–1480.PubMedGoogle Scholar
  67. Olsen, R. W., and Venter, J. C., eds., 1986, Receptor Biochemistry and Methodology, Volume 5, Benzodiazepine/GABA Receptors and Chloride Channels: Structural and Functional Properties, Alan R. Liss, New York.Google Scholar
  68. Olsen, R. W., Wamsley, J. K., McCabe, R. T., Lee, R. J., and Lomax, P., 1985, Benzodiazepine/;gg-aminobutyric acid receptor deficit in the midbrain of the seizure-susceptible gerbil, Proc. Natl. Acad. Sci. 82:6701–6705.PubMedCrossRefGoogle Scholar
  69. Ondrusek, M. G., Belknap, J. K., and Leslie, S. W., 1979, Effects of acute and chronic barbiturate administration on synaptosomal calcium accumulation, Mol. Pharmacol. 15:386–395.PubMedGoogle Scholar
  70. PDR, 1989, Product Information, in: Physician’s Desk Reference, Medical Economics, Oradell, NJ.Google Scholar
  71. Phillips, T. J., and Gallaher, E. J., 1988, Ethanol and diazepam effects on locomotor activity in mice selectively bred for diazepam sensitivity, in: Biomedical and Social Aspects of Alcohol and Alcoholism (D. Kuriyama, A. Takada, and H. Ishii, eds.), Excerpta Medica, New York, pp. 251–254.Google Scholar
  72. Pritchett, D. B., Sontheimer, H., Shivers, B. D., Ymer, S., Kettenmann, H., Schofield, P. R., and Seeburg, P. H., 1989a, Importance of a novel GABAA receptor subunit for benzodiazepine pharmacology, Nature 338:582–585.PubMedCrossRefGoogle Scholar
  73. Pritchett, D. B., Luddens, H., and Seeburg, P. H., 1989b, Type I and Type II GABAA-benzodiazepine receptors produced in transfected cells, Science 245:1389–1392.PubMedCrossRefGoogle Scholar
  74. Propping, P., Friedl, W., Hebebrand, J., and Lentes, K. U., 1986, Genetic studies at the receptor level: Investigations in human twins and experimental animals, Ciba Found. Symp. 123:42–56.PubMedGoogle Scholar
  75. Randall, C. L., and Lester, D., 1974, Differential effects of ethanol and pentobarbital on sleep times in C57BL and BALB mice, J. Pharmacol. Exp. Ther. 188:27–33.PubMedGoogle Scholar
  76. Ribak, C. E., Roberts, R. C., Byun, M. Y., and Kim, H. L., 1988, Anatomical and behavioral analyses of the inheritance of audiogenic seizures in the progeny of genetically epilepsy-prone and Sprague-Dawley rats, Epilepsy Res. 2:345–355.PubMedCrossRefGoogle Scholar
  77. Roberts, R. C., and Ribak, C. E., 1986, Anatomical changes of the GABAergic system in the inferior colliculus of the genetically epilepsy-prone rat, Life Sci. 39:789–798.PubMedCrossRefGoogle Scholar
  78. Robertson, H. A., 1979, Benzodiazepine receptors in “emotional” and “non-emotional” mice: Comparison of four strains, Eur. J. Pharmacol. 56:163–166.PubMedCrossRefGoogle Scholar
  79. Robertson, H. A., Martin, I. L., and Candy, J. M., 1978, Differences in benzodeiazepine receptor binding in Maudsley reactive and Maudsley non-reactive rats, Eur. J. Pharmacol. 50:455–457.PubMedCrossRefGoogle Scholar
  80. Schmitz, E., Friedl, W., Reichelt, R., and Hebebrand, J., 1988, Persistence of species variation and regional heterogeneity of the apparent molecular masses of benzodiazepine-binding proteins after deglycosylation, FEBS Lett. 237:199–202.PubMedCrossRefGoogle Scholar
  81. Schofield, P. R., Darlison, M. G., Fujita, N., Burt, D. R., Stephenson, F. A., Rodrigurz, H., Rhee, L. M., Ramachandran, J., Reale, V., Glencourse, T. A., Seeburg, P. H., and Barnard, E. A., 1987, Sequence and functional expression of the GABA receptor shows a ligand-gated receptor super-family, Nature 328:221–227.PubMedCrossRefGoogle Scholar
  82. Schwartz, R. D., Seale, T. W., Skolnick, P., and Paul, S. M., 1989, Differential seizure sensitivities to picrotoxinin in two inbred strains of mice (DBA/2J and BALB/c ByJ): Parallel changes in GABA receptor-mediated chloride flux and receptor binding, Brain Res. 481:169–174.PubMedCrossRefGoogle Scholar
  83. Schweri, M. M., Paul, S. M., and Skoknick, P., 1983, Strain differences in susceptibility to the convulsant actions of 3-carbomethoxy-beta-carboline, Pharmacol. Biochem. Behav. 19:951–955.PubMedCrossRefGoogle Scholar
  84. Seale, T. W., Carney, J. M., Rennert, O. M., Flux, M., and Skolnick, P., 1987a, Coincidence of seizure susceptibility to caffeine and to the benzodiazepine inverse agonist, DMCM, in SWR and CBA inbred mice, Pharmacol. Biochem. Behav. 26:381–387.PubMedCrossRefGoogle Scholar
  85. Seale, T. W., Abla, K. A., Roderick, T. H., Rennert, O. M., and Carney, J. M., 1987b, Different genes specify hyporesponsiveness to seizures induced by caffeine and the benzodiazepine inverse agonist, DMCM, Pharmacol. Biochem. Behav. 27:451–456.PubMedCrossRefGoogle Scholar
  86. Shepard, R. A., Nielsen, F. B., and Broadhurst, P. L., 1982, Sex and strain differences in benzodiazepine receptor binding in Roman rat strains, Eur. J. Pharmacol. 77:327–330.CrossRefGoogle Scholar
  87. Short, T. G., Forrest, P., and Galletly, D. C., 1987, Paradoxical reactions to benzodiazepines-a genetically determined phenomenon? Aneasth Intens Care 15:330–331.Google Scholar
  88. Siemens, A. J., and Chan, A. W. K., 1976, Differential effects of pentobarbital and ethanol in mice, Life Sci. 19:581–590.PubMedCrossRefGoogle Scholar
  89. Squires, R. F., ed., 1988, GABA and Benzodiazepine Receptors, CRC Press, Boca Raton, FL.Google Scholar
  90. Squires, R. F., and Braestrup, C., 1977, Benzodiazepine receptors in rat brain, Nature 266:732–734.PubMedCrossRefGoogle Scholar
  91. Stinchcomb, A., Bowers, B. J., and Wehner, J. M., 1989, The effects of ethanol and Ro 15-4513 on elevated plus-maze and rotarod performance in long-sleep and short-sleep mice, Alcohol 6:369–376.PubMedCrossRefGoogle Scholar
  92. Suzuki, T., Koike, Y., Yanaura, S., George, F. R., and Meisch, R. A., 1987, Genetic differences in the development of physical dependence on pentobarbital in four inbred strains of rats, Jpn. J. Pharmacol. 45:479–486.PubMedCrossRefGoogle Scholar
  93. Suzuki, T., Otani, K., Koike, Y., Motegi, H., and Misawa, M., 1988, Genetic differences in physical dependence on ethanol and barbital between two inbred strains of rats, in: Genetic Aspects of Alcoholism (K. Kiianmaa, B. Tabakoff, and T. Saito, eds.), Finnish Foundation for Alcohol Studies, Helsinki, pp. 157–165.Google Scholar
  94. Suzuki, T., Lu, M.-S., Motegi, H., and Misawa, M., 1990, Physical dependence on diazepam in Lewis and Fisher 344 inbred rat strains, Eur. J. Pharmacol. 183:1983.CrossRefGoogle Scholar
  95. Syapin, P. J., 1983, Inhibition of pentylenetetrazol induced genetically-determined stereotypic convulsions in tottering mutant mice by diazepam, Pharmacol. Biochem. Behav. 18:389–394.PubMedCrossRefGoogle Scholar
  96. Vesell, E. S., 1968, Factors altering the responsiveness of mice to hexobarbital, Pharmacology 1:81–97.PubMedCrossRefGoogle Scholar
  97. Vogel, J. R., Beer, B., and Clody, D. E., 1971, A simple and reliable conflict procedure for testing anti-anxiety agents, Psychopharmacology 21:1–7.CrossRefGoogle Scholar
  98. White, W. F., and Heller, A. H., 1982, Glycine receptor alteration in the mutant mouse spastic, Nature 298:655–657.PubMedCrossRefGoogle Scholar
  99. Wilks, L., File, S. E., and Martin, I. L., 1987, Evidence of strain differences in GABA-benzodiazepine coupling, Psychopharmacology 93:127–132.PubMedCrossRefGoogle Scholar
  100. Wong, P. T.-H., Yoong, Y. L., and Gwee, M. C. E., 1986, Marked variation in diazepam sensitivity in Swiss albino mice, Life Sci. 39:945–952.PubMedCrossRefGoogle Scholar
  101. Yoong, Y. L., and Wong, P. T.-H., 1988, Selective breeding of mice for differential sensitivity to diazepam, Behav. Genet. 18:185–191.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • Edward J. Gallaher
    • 1
  • John C. CrabbeJr.
    • 1
  1. 1.Research Service, Department of Veterans Affairs Medical Center and Departments of Medical Psychology and PharmacologyOregon Health Sciences UniversityPortlandUSA

Personalised recommendations