Psychopharmacology

, Volume 103, Issue 2, pp 154–161 | Cite as

Self-injection of barbiturates, benzodiazepines and other sedative-anxiolytics in baboons

  • Roland R. Griffiths
  • R. J. Lamb
  • Christine A. Sannerud
  • Nancy A. Ator
  • Joseph V. Brady
Original Investigations

Abstract

Self-injection of 12 sedative-anxiolytics was examined in baboons. Intravenous injections and initiation of a 3-h time-out were dependent upon completion of a fixed-ratio schedule requirement, permitting eight injections per day. Before testing each dose of drug, self-injection performance was established with cocaine. Subsequently, a test dose was substituted for cocaine. At some doses, all five of the benzodiazepines examined (alprazolam, bromazepam, chlordiazepoxide, lorazepam, triazolam) maintained rates (number of injections per day) of drug self-injection above vehicle control in each of the baboons tested. Maximum rates of benzodiazepine self-injection were generally submaximal. Of the benzodiazepines examined, triazolam maintained the highest rates of self-injection. Among the three barbiturates tested, methohexital generally maintained high rates of self-injection in contrast to hexobarbital and phenobarbital, which only maintained low rates. Of the four non-benzodiazepine non-barbiturate sedatives examined, both chloral hydrate and methyprylon occasionally maintained high rates of self-injection. Although there were differences within and across animals, baclofen maintained intermediate rates of self-injection. The novel anxiolytic buspirone maintained only low rates of self-injection that were not different from vehicle. This study further validates the self-injection methodology for assessing sedative-anxiolytic abuse liability and provides new information about drug elimination rate as a determinant of drug self-administration.

Key words

Benzodiazepines Barbiturates Anxiolytics Drug abuse Baboons 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ator NA, Griffiths RR (1983) Oral self-administration of methohexital in baboons. Psychopharmacology 79:120–125Google Scholar
  2. Ator NA, Griffiths RR (1987) Self-administration of barbiturates and benzodiazepines: a review. Pharmacol Biochem Behav 27:391–398Google Scholar
  3. Balster RL, Woolverton WL (1982) Intravenous buspirone self-administration in rhesus monkeys. J Clin Psychiatry 43:34–37Google Scholar
  4. Bianchine JR (1985) Drugs for Parkinson's disease, spasticity, and acute muscle spasms. In: Gilman AG, Goodman LS, Rall TW, Murad F (eds) The pharmacological basis of therapeutics. Macmillan, New York, pp 473–490Google Scholar
  5. Busto U, Simpkins J, Sellers EM, Sisson B, Segal R (1983) Objective determination of benzodiazepine use and abuse in alcoholics. Br J Addict 78:429–435Google Scholar
  6. Carroll ME, Stotz DC, Kliner DJ, Meisch RA (1984) Self-administration of orally-delivered methohexital in rhesus monkeys with phencyclidine or pentobarbital histories: effects of food deprivation and satiation. Pharmacol Biochem Behav 20:145–151Google Scholar
  7. Cole JO, Orzack MH, Beake B, Bird M, Bar-Tal Y (1982) Assessment of the abuse liability of buspirone in recreational sedative users. J Clin Psychiatry 43:69–74Google Scholar
  8. Collins RJ, Weeks JR, Cooper MM, Good PI, Russell RR (1984) Prediction of abuse liability of drugs using IV self-administration by rats. Psychopharmacology 82:6–13Google Scholar
  9. Davis JD, Lulenski GC, Miller NE (1968) Comparative studies of barbiturate self-administration. Int J Addict 3:207–214Google Scholar
  10. Dupont RL (1988) Abuse of benzodiazepines: the problems and the solutions. Am J Drug Alcohol Abuse [Suppl. 1] 14:1–69Google Scholar
  11. Findley JD, Robinson WW, Gilliam W (1971) A restraint system for chronic study of the baboon. J Exp Anal Behav 15:69–71Google Scholar
  12. Findley JD, Robinson WW, Peregrino L (1972) Addiction to secobarbital and chlordiazepoxide in the rhesus monkey by means of a self-infusion preference procedure. Psychopharmacologia 26:93–114Google Scholar
  13. Fraser HF, Jasinski DR (1977) In: Martin WR (ed) Handbook of experimental pharmacology, vol 45. Springer, Berlin Heidelberg New York, pp 589–612Google Scholar
  14. Griffith JD, Jasinski DR, Casten GP, McKinney GR (1986) Investigation of the abuse liability of buspirone in alcohol-dependent patients. Am J Med [Suppl 3B] 80:30–35Google Scholar
  15. Griffiths RR, Bigelow GE, Henningfield JE (1980) In: Mello NK (ed) Advances in substance abuse: behavioral and biological research. JAI Press, Greenwich, Connecticut, pp 1–90Google Scholar
  16. Griffiths RR, Sannerud CA (1987) Abuse of and dependence on benzodiazepines and other anxiolytic/sedative drugs. In: Meltzer HY (ed) Psychopharmacology the third generation of progress. Raven Press, New York, pp 1535–1541Google Scholar
  17. Griffiths RR, Wolf B (1990) Relative abuse liability of different benzodiazepines in drug abusers. J Clin Psychopharmacol 10:237–243Google Scholar
  18. Griffiths RR, Findley JD, Brady JV, Dolan-Gutcher K, Robinson WW (1975) Comparison of progressive-ratio performance maintained by cocaine, methylphenidate and secobarbital. Psychopharmacologia 43:81–83Google Scholar
  19. Griffiths RR, Lamb RJ, Ator NA, Roache JD, Brady JV (1985) Relative abuse liability of triazolam: experimental assessment in animals and humans. Neurosci Biobehav Rev 9:133–151Google Scholar
  20. Griffiths RR, Lukas SE, Bradford LD, Brady JV, Snell JD (1981) Self-injection of barbiturates and benzodiazepines in baboons. Psychopharmacology 75:101–109Google Scholar
  21. Harvey SC (1975) Hypnotics and sedatives: the barbiturates. In: Goodman LS, Gilman A (eds) The pharmacological basis of therapeutics. Macmillan, New York, pp 102–124Google Scholar
  22. Hulinder B, Östman O (1987) Baklofen — nytt medel i missbrukarkretsar [Baclofen — a new agent used by addicts]. Läkartidningen 84:3726Google Scholar
  23. Jaffe JH (1975) Drug addiction and drug abuse. In: Goodwin LS, Gilman A (eds) The pharmacological basis of therapeutics. Macmillan, New York, pp 284–324Google Scholar
  24. Johanson CE (1987) Benzodiazepine self-administration in rhesus monkeys: estazolam, flurazepam and lorazepam. Pharmacol Biochem Behav 26:521–526Google Scholar
  25. Johanson CE, Balster RL (1978) A summary of the results of a drug self-administration study using substitution procedures in rhesus monkeys. Bull Narc 30:43–54Google Scholar
  26. Johanson CE, Schuster CR (1986) The effects of Ro 15–1788 on anxiolytic self-administration in the rhesus monkey. Pharmacol Biochem Behav 24:855–859Google Scholar
  27. Kelleher RT (1975) Characteristics of behavior controlled by scheduled injections of drugs. Pharmacol Rev 27:307–323Google Scholar
  28. Kubota A, Kuwahara A, Hakkei M, Nakamura K (1986) Drug dependence tests on a new anesthesia inducer, midazolam. Folia Pharmacol Jpn 88:125–158Google Scholar
  29. Lukas SE, Griffiths RR (1982) Comparison of triazolam and diazepam self-administration by the baboon. Pharmacologist 24:133Google Scholar
  30. Lukas SE, Griffiths RR, Bradford LD, Brady JV, Daley L, DeLorenzo R (1982) A tethering system for intravenous and intragastric drug administration in the baboon. Pharmacol Biochem Behav 17:823–829Google Scholar
  31. May CR (1983) Baclofen overdose. Annals of Emergency Medicine 12:171–173Google Scholar
  32. National Institute on Drug Abuse (1989) National household survey on drug abuse: population estimates 1988, DHHS (ADM)89-1636, US Government Printing Office, Washington DCGoogle Scholar
  33. Pickens R, Muchow D, DeNoble V (1981) Methohexital-reinforced responding in rats: effects of fixed ratio size and injection dose. J Pharmacol Exp Ther 216:205–209Google Scholar
  34. Robinson JT (1966) A case of chloral hydrate addiction. Int J Soc Psychiatry 12:66–71Google Scholar
  35. Schutz H (1982) Benzodiazepines — a handbook: basic data, analytical methods, pharmacokinetics and comprehensive literature. Springer, Berlin Heidelberg New YorkGoogle Scholar
  36. Schutz H (1989) Benzodiazepines II — a handbook: basic data, analytical methods, pharmacokinetics and comprehensive literature. Springer, Berlin Heidelberg New York Springer, Berlin Heidelberg New YorkGoogle Scholar
  37. Traber J, Glaser T (1987) 5-HT1A receptor-related anxiolytics. TIPS 8:432–437Google Scholar
  38. Wesson DR, Smith DE (1977) Barbiturates: their use misuse, and abuse. Human Sciences Press, New YorkGoogle Scholar
  39. Winger G, Stitzer ML, Woods JH (1975) Barbiturate-reinforced responding in rhesus monkeys: comparison of drugs with different durations of actions. J Pharmacol Exp Ther 195:505–514Google Scholar
  40. Woods JH, Katz JL, Winger G (1987) Abuse liability of benzodiazepines. Pharmacol Rev 39:251–419Google Scholar

Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • Roland R. Griffiths
    • 1
    • 2
  • R. J. Lamb
    • 1
  • Christine A. Sannerud
    • 1
  • Nancy A. Ator
    • 1
  • Joseph V. Brady
    • 1
    • 2
  1. 1.Department of Psychiatry and Behavioral SciencesThe Johns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Department of NeuroscienceThe Johns Hopkins University School of MedicineBaltimoreUSA

Personalised recommendations