Skip to main content
SpringerLink
Log in

Tolerance and sensitization to inhaled 1,1,1-trichloroethane in mice: results from open-field behavior and a functional observational battery

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

1,1,1-Trichloroethane (TCE), a representative abused solvent, has well described acute behavioral effects in animals. Much less is known about repeated high-concentration exposures as would be encountered in inhalant abusers. Tolerance has been demonstrated in some, but not all, studies with TCE while sensitization has also been seen with other abused solvents.

Objective

The present study was designed to further characterize changes in the effects of repeated exposure to TCE on a variety of mouse behaviors.

Methods

Mice were tested using locomotor activity as well as a functional observational battery (FOB) both before and after a regimen of daily exposures to various concentrations of TCE.

Results

The initial locomotor effects of acute 30-min exposures to TCE were biphasic with concentration-dependent increases in activity at lower concentrations and decreases observed at higher concentrations. The profile of acute effects as measured by the FOB included changes in posture, decreased arousal, disturbances in gait, delayed righting reflexes, and decreased sensorimotor reactivity. Animals were then divided into five groups and exposed 30 min/day to either air or one of four concentrations of TCE (2,000, 6,000, 10,000, or 13,300 ppm) for 15 consecutive days. The TCE concentration used primarily affected the magnitude of change, not whether tolerance or sensitization occurred. Tolerance developed on the measures of forelimb grip strength, inverted screen, and number of rears. Conversely, sensitization developed to measures of locomotor activity.

Conclusion

Depending on the behavioral measure, both tolerance and sensitization can occur in mice with repeated exposure to TCE. Both of these phenomena are characteristic of drugs of abuse.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Balster RL (1987) Abuse potential evaluation of inhalants. Drug Alcohol Depend 19:7–15

    Article  PubMed  CAS  Google Scholar 

  • Balster RL (1998) Neural basis of inhalant abuse. Drug Alcohol Depend 51:207–214

    Article  PubMed  CAS  Google Scholar 

  • Beyer CE, Stafford D, LeSage MG, Glowa JR, Steketee JD (2001) Repeated exposure to inhaled toluene induces behavioral and neurochemical cross-sensitization to cocaine in rats. Psychopharmacology 154:198–204

    Article  PubMed  CAS  Google Scholar 

  • Bowen SE, Balster RL (1996) Effects of inhaled 1,1,1-trichloroethane on locomotor activity in mice. Neurotoxicol Teratol 18:77–81

    Article  PubMed  CAS  Google Scholar 

  • Bowen SE, Balster RL (1997) Tolerance to the anxiolytic effects of diazepam and toluene as measured by an elevated plus-maze task in mice. Soc Neurosci Abstr 23:2395

    Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Bowen SE, Wiley JL, Balster RL (1996a) The effects of abused inhalants on mouse behavior in an elevated plus-maze. Eur J Pharmacol 312:131–136

    Article  PubMed  CAS  Google Scholar 

  • Bowen SE, Wiley JL, Evans EB, Tokarz ME, Balster RL (1996b) Functional observational battery comparing effects of ethanol, 1,1,1-trichloroethane, ether, and flurothyl. Neurotoxicol Teratol 18:577–585

    Article  PubMed  CAS  Google Scholar 

  • Bushnell PJ, Oshiro WM (2000) Behavioral components of tolerance to repeated inhalation of trichloroethylene (TCE) in rats. Neurotoxicol Teratol 22:221–229

    Article  PubMed  CAS  Google Scholar 

  • Castilla-Serna L, Barragan-Mejia MG, Rodriguez-Perez RA, Garcia Rillo A, Reyes-Vazquez C (1993) Effects of acute and chronic toluene inhalation on behavior, monoamine metabolism and specific binding (3H-serotonin and 3H-norepinephrine) of rat brain. Arch Med Res 24:169–176

    PubMed  CAS  Google Scholar 

  • Evans AC, Raistrick D (1987) Phenomenology of intoxication with toluene-based adhesives and butane gas. Br J Psychiatry 150:769–773

    PubMed  CAS  Google Scholar 

  • Evans EB, Balster RL (1991) CNS depressant effects of volatile organic solvents. Neurosci Biobehav Rev 15:233–241

    Article  PubMed  CAS  Google Scholar 

  • Forster LM, Tannhauser M, Tannhauser SL (1994) Toxicology of toluene: aspects related to its abuse. Rev Saude Publica 28:167–172

    PubMed  CAS  Google Scholar 

  • Glaser HH, Massengale ON (1962) Glue-sniffing in children. Deliberate inhalation of vaporized plastic cements. JAMA 181:300–303

    PubMed  CAS  Google Scholar 

  • Gralewicz S (1999) Organic solvents and time-dependent sensitization. Int J Occup Med Environ Health 12:371–381

    PubMed  CAS  Google Scholar 

  • Hinman DJ (1984) Tolerance and reverse tolerance to toluene inhalation: effects on open- field behavior. Pharmacol Biochem Behav 21:625–631

    Article  PubMed  Google Scholar 

  • Hinman DJ (1987) Biphasic dose–response relationship for effects of toluene inhalation on locomotor activity. Pharmacol Biochem Behav 26:65–69

    Article  PubMed  CAS  Google Scholar 

  • Johnston LD, O’Malley PM, Bachman JG, Schulenberg JE (2004) Overall teen drug use continues gradual decline; but use of inhalants rises. University of Michigan News and Information Services, Ann Arbor, MI

    Google Scholar 

  • Kalant H (1989) Drug tolerance and sensitization: a pharmacological review. In: Goudie AJ, Emmett-Oglesby MW (eds) Psychoactive drugs: tolerance and sensitization. Humana, Clifton, NJ, pp 547–577

    Chapter  Google Scholar 

  • Kalivas PW, Stewart J (1991) Dopamine transmission in the initiation and expression of drug- and stress-induced sensitization of motor activity. Brain Res Rev 16:223–244

    Article  PubMed  CAS  Google Scholar 

  • Kuczenski R, Segal DS (2001) Locomotor effects of acute and repeated threshold doses of amphetamine and methylphenidate: relative roles of dopamine and norepinephrine. J Pharmacol Exp Ther 296:876–883

    PubMed  CAS  Google Scholar 

  • McDougall SA, Collins RL, Karper PE, Watson JB, Crawford CA (1999) Effects of repeated methylphenidate treatment in the young rat: sensitization to both locomotor activity and stereotyped sniffing. Exp Clin Psychopharmacol 7:208–218

    Article  PubMed  CAS  Google Scholar 

  • Mitoma C, Steeger T, Jackson SE, Wheeler KP, Rogers JH, Milman HA (1985) Metabolic disposition study of chlorinated hydrocarbons in rats and mice. Drug Chem Toxicol 8:183–194

    Article  PubMed  CAS  Google Scholar 

  • Monster AC, Boersma G, Steenweg H (1979) Kinetics of 1,1,1-trichloroethane in volunteers: influence of exposure concentration and work load. Int Arch Occup Environ Health 42:293–301

    Article  PubMed  CAS  Google Scholar 

  • Moser VC, Balster RL (1981) The effects of acute and repeated toluene exposure on operant behavior in mice. Neurobehav Toxicol Teratol 3:471–475

    PubMed  CAS  Google Scholar 

  • Moser VC, Scimeca, JA, Balster RL (1985) Minimal tolerance to the effects of 1,1,1-trichloroethane on fixed-ratio responding in mice. Neurotoxicology 6:35–42

    CAS  PubMed  Google Scholar 

  • Nolan RJ, Freshour NL, Rick DL, McCarty LP, Saunders JH (1984) Kinetics and metabolism of inhaled methyl chloroform (1,1,1-trichloroethane) in male volunteers. Fundam Appl Toxicol 4:654–662

    Article  PubMed  CAS  Google Scholar 

  • Novak A (1980) The deliberate inhalation of volatile substances. J Psychedelic Drugs 12:105–122

    PubMed  CAS  Google Scholar 

  • Oshiro WM, Krantz QT, Bushnell PJ (2001) Characterizing tolerance to trichloroethylene (TCE): effects of repeated inhalation of TCE on performance of a signal detection task in rats. Neurotoxicol Teratol 23:617–628

    Article  PubMed  CAS  Google Scholar 

  • Pierce RC, Kalivas PW (1997) A circuitry model of the expression of behavioral sensitization to amphetamine-like psychostimulants. Brain Res Rev 25:192–216

    Article  PubMed  CAS  Google Scholar 

  • Poet TS, Thrall KD, Corley RA, Hui X, Edwards JA, Weitz KK, Maibach HI, Wester RC (2000) Utility of real time breath analysis and physiologically based pharmakokinetic modeling to determine the percutaneous absorption of methyl chloroform in rats and humans. Toxicol Sci 54:42–51

    Article  PubMed  CAS  Google Scholar 

  • Ramon MF, Ballesteros S, Martinez-Arrieta R, Torrecilla JM, Cabrera J (2003) Volatile substance and other drug abuse inhalation in Spain. J Toxicol Clin Toxicol 41:931–936

    Article  PubMed  CAS  Google Scholar 

  • Rees DC, Wood RW, Laties VG (1989) Evidence of tolerance following repeated exposure to toluene in the rat. Pharmacol Biochem Behav 32:283–291

    Article  PubMed  CAS  Google Scholar 

  • Riegel AC, French ED (1999) Acute toluene induces biphasic changes in rat spontaneous locomotor activity which are blocked by remoxipride. Pharmacol Biochem Behav 62:399–402

    Article  PubMed  CAS  Google Scholar 

  • Riegel AC, French ED (2002) Abused inhalants and central reward pathways: electrophysiological and behavioral studies in the rat. Ann NY Acad Sci 965:281–291

    Article  PubMed  CAS  Google Scholar 

  • Riegel AC, Ali SF, French ED (2003) Toluene-induced locomotor activity is blocked by 6-hydroxydopamine lesions of the nucleus accumbens and the mGluR2/3 agonist LY379268. Neuropsychopharmacology 28:1440–1447

    Article  PubMed  CAS  Google Scholar 

  • Robinson TE (1993) Persistent sensitizing effects of drugs on brain dopamine systems and behavior: implications for addiction and relapse. In: Korenman SG, Barchas JD (eds) Biological basis of substance abuse. Oxford Univ. Press, New York, pp 373–402

    Google Scholar 

  • Rogers WR, Miller CS, Bunegin L (1999) A rat model of neurobehavioral sensitization to toluene. Toxicol Ind Health 15:356–369

    Article  PubMed  CAS  Google Scholar 

  • Schumann AM, Fox TR, Watanabe PG (1982a) A comparison of the fate of inhaled methyl chloroform (1,1,1-trichloroethane) following single or repeated exposure in rats and mice. Fundam Appl Toxicol 2:27–32

    Article  PubMed  CAS  Google Scholar 

  • Schumann AM, Fox TR, Watanabe PG (1982b) [14C] methyl chloroform (1,1,1-trichloroethane): pharmacokinetics in rats and mice following inhalation exposure. Toxicol Appl Pharmacol 62:390–401

    Article  PubMed  CAS  Google Scholar 

  • Schuster CR, Dockens WS, Woods JH (1966) Behavioral variables affecting the development of amphetamine tolerance. Psychopharmacology 9:170–182

    Article  CAS  Google Scholar 

  • Taylor JD, Evans HL (1985) Effects of toluene inhalation on behavior and expired carbon dioxide in macaque monkeys. Toxicol Appl Pharmacol 80:487–495

    Article  PubMed  CAS  Google Scholar 

  • Tegeris JS, Balster RL (1994) A comparison of the acute behavioral effects of alkylbenzenes using a functional observational battery in mice. Fundam Appl Toxicol 22:240–250

    Article  PubMed  CAS  Google Scholar 

  • Thiesen FV, Barros HM (2004) Measuring inhalant abuse among homeless youth in southern Brazil. J Psychoactive Drugs 36:201–205

    PubMed  Google Scholar 

  • Waraich BK, Chavan BS, Raj L (2003) Inhalant abuse: a growing public health concern in India. Addiction 98:1169

    Article  CAS  PubMed  Google Scholar 

  • Warren DA, Bowen SE, Jennings WB, Dallas CE, Balster RL (2000) Biphasic effects of 1,1,1-trichloroethane on the locomotor activity of mice: relationship to blood and brain solvent concentrations. Toxicol Sci 56:365–373

    Article  PubMed  CAS  Google Scholar 

  • Wiaderna D, Tomas T (2000) Effects of repeated exposure to toluene or amphetamine on locomotor activity in rats. Int J Occup Med Environ Health 13:317–324

    PubMed  CAS  Google Scholar 

  • Wiaderna D, Tomas T (2002) Assessment of long-term effects of exposure to toluene based on the analysis of selected behavioral responses with particular reference to the ability to trigger behavioral hypersensitivity in rats. Int J Occup Med Environ Health 15:239–245

    PubMed  Google Scholar 

  • Wiley JL, Fagalde RE, Buhler KG, LaVecchia KL, Balster RL (2002) Evaluation of 1,1,1-trichloroethane and flurothyl locomotor effects following diazepam treatment in mice. Pharmacol Biochem Behav 71:163–169

    Article  PubMed  CAS  Google Scholar 

  • Wolgin DL (1989) The role of instrumental learning in behavioral tolerance to drugs. In: Goudie AJ, Emmett-Oglesby MW (eds) Psychoactive drugs: tolerance and sensitization. Humana, Clifton, New Jersey, pp 17–114

    Chapter  Google Scholar 

  • Wood RW, Colotla VA (1990) Biphasic changes in mouse motor activity during exposure to toluene. Fundam Appl Toxicol 14:6–14

    Article  PubMed  CAS  Google Scholar 

  • Woolverton WL, Balster RL (1981) Behavioral and lethal effects of combinations of oral ethanol and inhaled 1,1,1-trichloroethane in mice. Toxicol Appl Pharmacol 59:1–7

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors wish to thank Mary Tokarz for her technical assistance during the execution and analysis of this study. This research was supported by National Institute on Drug Abuse (NIDA) grants DA03112 to RLB and DA15095 to SEB.

Author information

Authors and Affiliations

  1. Department of Psychology, Wayne State University, 5057 Woodward Ave., Detroit, MI, 48202, USA

    Scott E. Bowen

  2. Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, VA, 23298-0310, USA

    Robert L. Balster

Authors
  1. Scott E. Bowen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert L. Balster
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Scott E. Bowen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bowen, S.E., Balster, R.L. Tolerance and sensitization to inhaled 1,1,1-trichloroethane in mice: results from open-field behavior and a functional observational battery. Psychopharmacology 185, 405–415 (2006). https://doi.org/10.1007/s00213-006-0335-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-006-0335-1

Keywords

Search

Navigation