Advertisement

Psychopharmacology

, Volume 231, Issue 7, pp 1339–1350 | Cite as

Assessment of reinforcement enhancing effects of toluene vapor and nitrous oxide in intracranial self-stimulation

  • Matthew E. Tracy
  • Galina G. Slavova-Hernandez
  • Keith L. SheltonEmail author
Original Investigation

Abstract

Rationale

Despite widespread abuse, there are few validated methods to study the rewarding effects of inhalants. One model that may have utility for this purpose is intracranial self-stimulation (ICSS).

Objectives

This study aims to compare and contrast the ICSS reward-facilitating effects of abused inhalants to other classes of abused drugs. Compounds were examined using two different ICSS procedures in mice to determine the generality of each drug’s effects on ICSS and the sensitivity of the procedures.

Methods

Male C57BL/6J mice with electrodes implanted in the medial forebrain bundle were trained under a three-component rate-frequency as well as a progressive ratio (PR) ICSS procedure. The effects of nitrous oxide, toluene vapor, cocaine, and diazepam on ICSS were then examined.

Results

Concentrations of 1,360–2,900 parts per million (ppm) inhaled toluene vapor significantly facilitated ICSS in the rate-frequency procedure and 1,360 ppm increased PR breakpoint. A concentration of 40 % nitrous oxide facilitated ICSS in the rate-frequency procedure but reduced PR breakpoint. Doses of 3–18 mg/kg cocaine facilitated ICSS in the rate-frequency procedure, and 10 and 18 mg/kg increased PR breakpoint. Doses of 1 and 3 mg/kg diazepam facilitated ICSS in the rate-frequency procedure, and 3 mg/kg increased PR breakpoint.

Conclusions

The reinforcement-facilitating effect of toluene in ICSS is at least as great as diazepam. By contrast, nitrous oxide weakly enhances ICSS in only the rate-frequency procedure. The data suggest that the rate-frequency procedure may be more sensitive than the PR schedule to the reward-facilitating effects of abused inhalants.

Keywords

Rate-frequency ICSS Intracranial self-stimulation Mice Inhalant Toluene Nitrous oxide Diazepam Progressive ratio Cocaine 

Notes

Funding

This study is funded by National Institute of Drug Abuse grant no. R01DA-020553 and F31DA034469.

Conflict of interest

None.

References

  1. Altarifi AA, Negus SS (2011) Some determinants of morphine effects on intracranial self-stimulation in rats: dose, pretreatment time, repeated treatment, and rate dependence. Behav Pharmacol 22:663–673. doi: 10.1097/FBP.0b013e32834aff54 PubMedCentralPubMedCrossRefGoogle Scholar
  2. Balster RL, Cruz SL, Howard MO et al (2009) Classification of abused inhalants. Addiction 104:878–882. doi: 10.1111/j.1360-0443.2008.02494.x PubMedCrossRefGoogle Scholar
  3. Bauer CT, Banks ML, Blough BE, Negus SS (2013) Use of intracranial self-stimulation to evaluate abuse-related and abuse-limiting effects of monoamine releasers in rats. Br J Pharmacol 168:850–862. doi: 10.1111/j.1476-5381.2012.02214.x PubMedCentralPubMedCrossRefGoogle Scholar
  4. Bespalov A, Sukhotina I, Medvedev I et al (2003) Facilitation of electrical brain self-stimulation behavior by abused solvents. Pharmacol Biochem Behav 75:199–208. doi: 10.1016/S0091-3057(03)00071-6 PubMedCrossRefGoogle Scholar
  5. Blednov YA, Borghese CM, McCracken ML et al (2011) Loss of ethanol conditioned taste aversion and motor stimulation in knockin mice with ethanol-insensitive α2-containing GABA(A) receptors. J Pharmacol Exp Ther 336:145–154. doi: 10.1124/jpet.110.171645 PubMedCentralPubMedCrossRefGoogle Scholar
  6. Blokhina EA, Dravolina OA, Bespalov AY et al (2004) Intravenous self-administration of abused solvents and anesthetics in mice. Eur J Pharmacol 485:211–218. doi: 10.1016/j.ejphar.2003.11.068 PubMedCrossRefGoogle Scholar
  7. Bonano JS, Glennon RA, De Felice LJ et al (2013) Abuse-related and abuse-limiting effects of methcathinone and the synthetic “bath salts” cathinone analogs methylenedioxypyrovalerone (MDPV), methylone and mephedrone on intracranial self-stimulation in rats. Psychopharmacology (Berl). doi: 10.1007/s00213-013-3223-5 Google Scholar
  8. Bowen SE, Balster RL (1998) A direct comparison of inhalant effects on locomotor activity and schedule-controlled behavior in mice. Exp Clin Psychopharmacol 6:235–247. doi: 10.1037/1064-1297.6.3.235 PubMedCrossRefGoogle Scholar
  9. Bowen SE, Hannigan JH (2006) Developmental toxicity of prenatal exposure to toluene. AAPS J 8:E419–E424. doi: 10.1007/BF02854915 PubMedCentralPubMedCrossRefGoogle Scholar
  10. Bowen SE, McDonald P (2009) Abuse pattern of toluene exposure alters mouse behavior in a waiting-for-reward operant task. Neurotoxicol Teratol 31:18–25. doi: 10.1016/j.ntt.2008.09.002 PubMedCentralPubMedCrossRefGoogle Scholar
  11. Bowen SE, Wiley JL, Balster RL (1996) The effects of abused inhalants on mouse behavior in an elevated plus-maze. Eur J Pharmacol 312:131–136. doi: 10.1016/0014-2999(96)00459-1 PubMedCrossRefGoogle Scholar
  12. Bowen SE, Kimar S, Irtenkauf S (2010) Comparison of toluene-induced locomotor activity in four mouse strains. Pharmacol Biochem Behav 95:249–257. doi: 10.1016/j.pbb.2010.01.014 PubMedCentralPubMedCrossRefGoogle Scholar
  13. Brouette T, Anton R (2001) Clinical review of inhalants. Am J Addict 10:79–94. doi: 10.1080/105504901750160529 PubMedCrossRefGoogle Scholar
  14. Carlezon WA, Chartoff EH (2007) Intracranial self-stimulation (ICSS) in rodents to study the neurobiology of motivation. Nat Protoc 2:2987–2995. doi: 10.1038/nprot.2007.441 PubMedCrossRefGoogle Scholar
  15. Chan M-H, Chung S-S, Stoker AK et al (2012) Sarcosine attenuates toluene-induced motor incoordination, memory impairment, and hypothermia but not brain stimulation reward enhancement in mice. Toxicol Appl Pharmacol 265:158–165. doi: 10.1016/j.taap.2012.10.004 PubMedCentralPubMedCrossRefGoogle Scholar
  16. Cho AM, Coalson DW, Klock PA et al (1997) The effects of alcohol history on the reinforcing, subjective and psychomotor effects of nitrous oxide in healthy volunteers. Drug Alcohol Depend 45:63–70PubMedCrossRefGoogle Scholar
  17. Collado V, Nicolas E, Faulks D, Hennequin M (2007) A review of the safety of 50 % nitrous oxide/oxygen in conscious sedation. Expert Opin Drug Saf 6:559–571. doi: 10.1517/14740338.6.5.559 PubMedCrossRefGoogle Scholar
  18. Cruz SL, Domínguez M (2011) Misusing volatile substances for their hallucinatory effects: a qualitative pilot study with Mexican teenagers and a pharmacological discussion of their hallucinations. Subst Use Misuse 46(Suppl 1):84–94. doi: 10.3109/10826084.2011.580222 PubMedCrossRefGoogle Scholar
  19. Cruz SL, Mirshahi T, Thomas B et al (1998) Effects of the abused solvent toluene on recombinant N-methyl-d-aspartate and non-N-methyl-d-aspartate receptors expressed in Xenopus oocytes. J Pharmacol Exp Ther 286:334–340PubMedGoogle Scholar
  20. Depoortere, Perrault G, Sanger DJ (1999) Intracranial self-stimulation under a progressive-ratio schedule in rats: effects of strength of stimulation, d-amphetamine, 7-OH-DPAT and haloperidol. Psychopharmacology (Berl) 142:221–229. doi: 10.1007/s002130050883 CrossRefGoogle Scholar
  21. Dews PB (1977) Rate-dependency hypothesis. Science 198:1182–1183. doi: 10.1126/science.563103 PubMedCrossRefGoogle Scholar
  22. Elkoussi A, Bakheet S (2011) Volatile substance misuse among street children in Upper Egypt. Subst Use Misuse 46(Suppl 1):35–39. doi: 10.3109/10826084.2011.580202 PubMedCrossRefGoogle Scholar
  23. Emmanouil DE, Johnson CH, Quock RM (1994) Nitrous oxide anxiolytic effect in mice in the elevated plus maze: mediation by benzodiazepine receptors. Psychopharmacology (Berl) 115:167–172. doi: 10.1007/BF02244768 CrossRefGoogle Scholar
  24. Fish EW, Riday TT, McGuigan MM et al (2010) Alcohol, cocaine, and brain stimulation-reward in C57Bl6/J and DBA2/J mice. Alcohol Clin Exp Res 34:81–89. doi: 10.1111/j.1530-0277.2009.01069.x PubMedCrossRefGoogle Scholar
  25. Garland EL, Howard MO, Perron BE (2009) Nitrous oxide inhalation among adolescents: prevalence, correlates, and co-occurrence with volatile solvent inhalation. J Psychoactive Drugs 41:337–347PubMedCentralPubMedGoogle Scholar
  26. Gupta SR, Palmer CA, Curé JK et al (2011) Toluene optic neurotoxicity: magnetic resonance imaging and pathologic features. Hum Pathol 42:295–298. doi: 10.1016/j.humpath.2010.08.005 PubMedCrossRefGoogle Scholar
  27. Hannigan JH, Bowen SE (2010) Reproductive toxicology and teratology of abused toluene. Syst Biol Reprod Med 56:184–200. doi: 10.3109/19396360903377195 PubMedCrossRefGoogle Scholar
  28. Hapfelmeier G, Zieglgänsberger W, Haseneder R et al (2000) Nitrous oxide and xenon increase the efficacy of GABA at recombinant mammalian GABA(A) receptors. Anesth Analg 91:1542–1549. doi: 10.1097/00000539-200012000-00045 PubMedCrossRefGoogle Scholar
  29. Hoet P, Lison D (2008) Ototoxicity of toluene and styrene: state of current knowledge. Crit Rev Toxicol 38:127–170. doi: 10.1080/10408440701845443 PubMedCrossRefGoogle Scholar
  30. Kornetsky C, Esposito RU, McLean S, Jacobson JO (1979) Intracranial self-stimulation thresholds: a model for the hedonic effects of drugs of abuse. Arch Gen Psychiatry 36:289–292PubMedCrossRefGoogle Scholar
  31. Lee DE, Gerasimov MR, Schiffer WK, Gifford AN (2006) Concentration-dependent conditioned place preference to inhaled toluene vapors in rats. Drug Alcohol Depend 85:87–90. doi: 10.1016/j.drugalcdep.2006.03.013 PubMedCrossRefGoogle Scholar
  32. Lin R-J, Chen H-F, Chang Y-C, Su J-J (2011) Subacute combined degeneration caused by nitrous oxide intoxication: case reports. Acta Neurol Taiwan 20:129–137PubMedGoogle Scholar
  33. Lo P-S, Chen H-H (2005) Immunohistochemical localization of toluene-induced c-Fos protein expression in the rat brain. Toxicol Lett 157:151–160, 16/j.toxlet.2005.01.014PubMedCrossRefGoogle Scholar
  34. Miyagawa M, Honma T, Sato M, Hasegawa H (1984) Conditioned taste aversion induced by toluene administration in rats. Neurobehav Toxicol Teratol 6:33–37PubMedGoogle Scholar
  35. Moser VC, Balster RL (1985) Effects of toluene, halothane and ethanol vapor on fixed-ratio performance in mice. Pharmacol Biochem Behav 22:797–802. doi: 10.1016/0091-3057(85)90530-1 PubMedCrossRefGoogle Scholar
  36. Moser VC, Balster RL (1986) The effects of inhaled toluene, halothane, 1,1,1-trichloroethane, and ethanol on fixed-interval responding in mice. Neurobehav Toxicol Teratol 8:525–531PubMedGoogle Scholar
  37. National Research Council (2011) Guide for the care and use of laboratory animals, 8th edn. National Academies Press, Washington, DCGoogle Scholar
  38. Paxinos G, Franklin KBJ (2001) The Mouse Brain in Stereotaxic Coordinates, 2nd edn. Academic Press, San DiegoGoogle Scholar
  39. Perit KE, Gmaz JM, Caleb Browne JD et al (2012) Distribution of c-Fos immunoreactivity in the rat brain following abuse-like toluene vapor inhalation. Neurotoxicol Teratol 34:37–46. doi: 10.1016/j.ntt.2011.10.007 PubMedCrossRefGoogle Scholar
  40. Ramsay DS, Watson CH, Leroux BG et al (2003) Conditioned place aversion and self-administration of nitrous oxide in rats. Pharmacol Biochem Behav 74:623–633. doi: 10.1016/S0091-3057(02)01048-1 PubMedCrossRefGoogle Scholar
  41. Reynolds LM, Engin E, Tantillo G et al (2012) Differential roles of GABA(A) receptor subtypes in benzodiazepine-induced enhancement of brain-stimulation reward. Neuropsychopharmacology 37:2531–2540. doi: 10.1038/npp.2012.115 PubMedCentralPubMedCrossRefGoogle Scholar
  42. Sharma S, Hryhorczuk C, Fulton S (2012) Progressive-ratio responding for palatable high-fat and high-sugar food in mice. J Vis Exp e3754. doi:  10.3791/3754
  43. Shelton KL (2009) Discriminative stimulus effects of inhaled 1,1,1-trichloroethane in mice: comparison to other hydrocarbon vapors and volatile anesthetics. Psychopharmacology (Berl) 203:431–440. doi: 10.1007/s00213-008-1380-8 CrossRefGoogle Scholar
  44. Shelton KL, Nicholson KL (2010) GABA(A) positive modulator and NMDA antagonist-like discriminative stimulus effects of isoflurane vapor in mice. Psychopharmacology (Berl) 212:559–569. doi: 10.1007/s00213-010-1979-4 CrossRefGoogle Scholar
  45. Shelton KL, Nicholson KL (2012) GABAA-positive modulator selective discriminative stimulus effects of 1,1,1-trichloroethane vapor. Drug Alcohol Depend 121:103–109. doi: 10.1016/j.drugalcdep.2011.08.016 PubMedCentralPubMedCrossRefGoogle Scholar
  46. Straub CJ, Carlezon WA Jr, Rudolph U (2010) Diazepam and cocaine potentiate brain stimulation reward in C57BL/6J mice. Behav Brain Res 206:17–20. doi: 10.1016/j.bbr.2009.08.025 PubMedCrossRefGoogle Scholar
  47. Tatum WO, Bui DD, Grant EG, Murtagh R (2010) Pseudo-Guillain–Barre syndrome due to “whippet”-induced myeloneuropathy. J Neuroimaging 20:400–401. doi: 10.1111/j.1552-6569.2009.00388.x PubMedCrossRefGoogle Scholar
  48. Tomasiewicz HC, Todtenkopf MS, Chartoff EH et al (2008) The kappa-opioid agonist U69,593 blocks cocaine-induced enhancement of brain stimulation reward. Biol Psychiatry 64:982–988. doi: 10.1016/j.biopsych.2008.05.029 PubMedCentralPubMedCrossRefGoogle Scholar
  49. Walker DJ, Zacny JP (2001) Within- and between-subject variability in the reinforcing and subjective effects of nitrous oxide in healthy volunteers. Drug Alcohol Depend 64:85–96. doi: 10.1016/S0376-8716(00)00234-9 PubMedCrossRefGoogle Scholar
  50. Walker DJ, Zacny JP (2003) Bitonic dose–response functions for reinforcing and self-reported effects of nitrous oxide in humans. Pharmacol Biochem Behav 74:851–857PubMedCrossRefGoogle Scholar
  51. Wise RA (1980) Action of drugs of abuse on brain reward systems. Pharmacol Biochem Behav 13(Suppl 1):213–223PubMedCrossRefGoogle Scholar
  52. Wise RA, Bauco P, Carlezon WA Jr, Trojniar W (1992) Self-stimulation and drug reward mechanisms. Ann N Y Acad Sci 654:192–198. doi: 10.1111/j.1749-6632.1992.tb25967.x PubMedCrossRefGoogle Scholar
  53. Wood RW, Grubman J, Weiss B (1977) Nitrous oxide self-administration by the squirrel monkey. J Pharmacol Exp Ther 202:491–499PubMedGoogle Scholar
  54. Yavich L, Zvartau E (1994) A comparison of the effects of individual organic solvents and their mixture on brain stimulation reward. Pharmacol Biochem Behav 48:661–664. doi: 10.1016/0091-3057(94)90328-X PubMedCrossRefGoogle Scholar
  55. Yücel M, Takagi M, Walterfang M, Lubman DI (2008) Toluene misuse and long-term harms: a systematic review of the neuropsychological and neuroimaging literature. Neurosci Biobehav Rev 32:910–926. doi: 10.1016/j.neubiorev.2008.01.006 PubMedCrossRefGoogle Scholar
  56. Zacny JP, Walker DJ, Derus LM (2008) Choice of nitrous oxide and its subjective effects in light and moderate drinkers. Drug Alcohol Depend 98:163–168. doi: 10.1016/j.drugalcdep.2008.06.001 PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Matthew E. Tracy
    • 1
  • Galina G. Slavova-Hernandez
    • 1
  • Keith L. Shelton
    • 1
    Email author
  1. 1.Department of Pharmacology and ToxicologyVirginia Commonwealth University School of MedicineRichmondUSA

Personalised recommendations