Display options
Cite
Kaiyala KJ, Chan B, Ramsay DS. Robust thermoregulatory overcompensation, rather than tolerance, develops with serial administrations of 70% nitrous oxide to rats. J Therm Biol. 2012;37(1):30-40doi: 10.1016/j.jtherbio.2011.10.004.
Kaiyala, K. J., Chan, B., & Ramsay, D. S. (2012). Robust thermoregulatory overcompensation, rather than tolerance, develops with serial administrations of 70% nitrous oxide to rats. Journal of thermal biology, 37(1), 30-40. https://doi.org/10.1016/j.jtherbio.2011.10.004
Kaiyala, Karl J, et al. "Robust thermoregulatory overcompensation, rather than tolerance, develops with serial administrations of 70% nitrous oxide to rats." Journal of thermal biology vol. 37,1 (2012): 30-40. doi: https://doi.org/10.1016/j.jtherbio.2011.10.004
Kaiyala KJ, Chan B, Ramsay DS. Robust thermoregulatory overcompensation, rather than tolerance, develops with serial administrations of 70% nitrous oxide to rats. J Therm Biol. 2012 Jan 01;37(1):30-40. doi: 10.1016/j.jtherbio.2011.10.004. PMID: 22247586; PMCID: PMC3255088.
Copy Download .nbib Format: NLM
Share it on

J Therm Biol. 2012 Jan 01;37(1):30-40. doi: 10.1016/j.jtherbio.2011.10.004.

Robust thermoregulatory overcompensation, rather than tolerance, develops with serial administrations of 70% nitrous oxide to rats.

Journal of thermal biology

Karl J Kaiyala, Ben Chan, Douglas S Ramsay

Affiliations

  1. Department of Dental Public Health Sciences, University of Washington, Seattle, WA, USA.

PMID: 22247586 PMCID: PMC3255088 DOI: 10.1016/j.jtherbio.2011.10.004

Abstract

Changes in typical whole-animal dependent variables following drug administration represent an integral of the drug's pharmacological effect, the individual's autonomic and behavioral responses to the resulting disturbance, and many other influences. An archetypical example is core temperature (T(c)), long used for quantifying initial drug sensitivity and tolerance acquisition over repeated drug administrations. Our previous work suggested that rats differing in initial sensitivity to nitrous oxide (N(2)O)-induced hypothermia would exhibit different patterns of tolerance development across N(2)O administrations. Specifically, we hypothesized that rats with an initially insensitive phenotype would subsequently develop regulatory overcompensation that would mediate an allostatic hyperthermic state, whereas rats with an initially sensitive phenotype would subsequently compensate to a homeostatic normothermic state. To preclude confounding due to handling and invasive procedures, a valid test of this prediction required non-invasive thermal measurements via implanted telemetric temperature sensors, combined direct and indirect calorimetry, and automated drug delivery to enable repeatable steady-state dosing. We screened 237 adult rats for initial sensitivity to 70% N(2)O-induced hypothermia. Thirty highly sensitive rats that exhibited marked hypothermia when screened and 30 highly insensitive rats that initially exhibited minimal hypothermia were randomized to three groups (n=10 each/group) that received: 1) twelve 90-min exposures to 70% N(2)O using a classical conditioning procedure, 2) twelve 90-min exposures to 70% N(2)O using a random control procedure for conditioning, or 3) a no-drug control group that received custom-made air. Metabolic heat production (via indirect calorimetry), body heat loss (via direct calorimetry) and T(c) (via telemetry) were simultaneously quantified during N(2)O and control gas administrations. Initially insensitive rats rapidly acquired (3(rd) administration) a significant allostatic hyperthermic phenotype during N(2)O administration whereas initially sensitive rats exhibited classical tolerance (normothermia) during N(2)O inhalation in the 4(th) and 5(th) sessions. However, the sensitive rats subsequently acquired the hyperthermic phenotype and became indistinguishable from initially insensitive rats during the 11(th) and 12th N(2)O administrations. The major mechanism for hyperthermia was a brisk increase in metabolic heat production. However, we obtained no evidence for classical conditioning of thermal responses. We conclude that the degree of initial sensitivity to N(2)O-induced hypothermia predicts the temporal pattern of thermal adaptation over repeated N(2)O administrations, but that initially insensitive and sensitive animals eventually converge to similar (and substantial) magnitudes of within-administration hyperthermia mediated by hyper-compensatory heat production.

References

  1. Science. 1978 Jul 7;201(4350):16-22 - PubMed
  2. Psychopharmacology (Berl). 2005 Aug;181(1):48-59 - PubMed
  3. J Appl Physiol (1985). 2006 Apr;100(4):1332-7 - PubMed
  4. Addiction. 1999 Aug;94(8):1113-24 - PubMed
  5. Anesthesiology. 2005 Oct;103(4):845-54 - PubMed
  6. Psychopharmacology (Berl). 2007 Apr;191(2):233-42 - PubMed
  7. Am J Physiol Regul Integr Comp Physiol. 2005 Mar;288(3):R692-701 - PubMed
  8. J Comp Physiol Psychol. 1978 Dec;92(6):1137-49 - PubMed
  9. Exp Clin Psychopharmacol. 2000 Aug;8(3):276-93 - PubMed
  10. Annu Rev Psychol. 2008;59:29-53 - PubMed
  11. Diabetes. 2004 Dec;53 Suppl 3:S6-S15 - PubMed
  12. N Engl J Med. 2009 Jul 16;361(3):302-3 - PubMed
  13. Eur J Appl Physiol. 2010 May;109(1):13-25 - PubMed
  14. Comp Biochem Physiol A Mol Integr Physiol. 2011 Mar;158(3):252-64 - PubMed
  15. Eur J Appl Physiol. 2010 May;109(1):5-11 - PubMed
  16. Nat Med. 1998 Apr;4(4):460-3 - PubMed
  17. Physiol Behav. 2011 Apr 18;103(1):79-85 - PubMed
  18. Eur J Appl Physiol. 2010 May;109(1):27-33 - PubMed
  19. Psychol Rev. 1997 Jan;104(1):170-93 - PubMed
  20. Psychopharmacology (Berl). 2007 Apr;191(2):243-51 - PubMed
  21. Science. 2002 Mar 1;295(5560):1664-9 - PubMed
  22. Neuropharmacology. 2007 Nov;53(6):733-40 - PubMed
  23. Diabetes. 2000 Sep;49(9):1525-33 - PubMed
  24. Alcohol Clin Exp Res. 1986 Jun;10(3):343-9 - PubMed
  25. J Exp Psychol Anim Behav Process. 2002 Jul;28(3):309-20 - PubMed

Publication Types

Grant support