Systems-level Adaptations Explain Chronic Tolerance Development to Nitrous Oxide Hypothermia in Young and Mature Rats

Overview

Journal Psychopharmacology (Berl)

Specialty Pharmacology

Date 2007 Jan 12

PMID 17216156

Citations 11

Authors

Karl J Kaiyala

Shehzad Butt

Douglas S Ramsay

Affiliations

Soon will be listed here.

Abstract

Rationale: Nitrous oxide (N(2)O) can initially lower core temperature (T (core)), but hypothermic tolerance develops with chronic administration. Therefore, one or both of T (core)'s controlling determinants, heat production (HP) and heat loss (HL), must adapt across repeated N(2)O administrations. Simultaneous measurements of HP, HL, and T (core) during chronic N(2)O administrations will elucidate this adaptive process and constitute a rigorous model for studying the systems-level dynamics of tolerance in both mature and young animals. This approach is justified by the need to better understand the increased vulnerability to addiction associated with adolescent drug use.

Objectives: The objective of the study was to measure HL and HP across repeated steady-state administrations of 60% N(2)O in young and mature rats.

Materials And Methods: Synchronous measurements of HP (indirect calorimetry), HL (direct calorimetry), and T (core) (telemetry) were obtained during 60% N(2)O administrations in adolescent (28-45 days, n = 11) and mature rats (>90 days, n = 8). Rats received five 90-min drug exposures (every other day).

Results: Compared to mature rats, adolescents initially exhibited greater hypothermia, but acquired tolerance more rapidly and actually developed hyperthermia during the fifth administration. In both groups, N(2)O consistently increased HL, but progressive increases of intrasessional HP over repeated administrations prevented hypothermia and subsequently promoted hyperthermia in adolescent rats.

Conclusions: Adolescent rats hyper-adapt to N(2)O hypothermia. Increases of intrasessional HP across N(2)O administrations explained both tolerance to N(2)O hypothermia and the unexpected hyperthermia observed in adolescents. These findings raise the possibility that the increased vulnerability to addiction associated with adolescent drug use involves a hyper-adaptive tolerance mechanism.

Citing Articles

Validation of an equation for energy expenditure that does not require the respiratory quotient.

Kaiyala K, Wisse B, Lighton J PLoS One. 2019; 14(2):e0211585.

PMID: 30707737 PMC: 6358081. DOI: 10.1371/journal.pone.0211585.

Concentration-related metabolic rate and behavioral thermoregulatory adaptations to serial administrations of nitrous oxide in rats.

Kaiyala K, Ramsay D PLoS One. 2018; 13(4):e0194794.

PMID: 29672605 PMC: 5909668. DOI: 10.1371/journal.pone.0194794.

Brown adipose tissue thermogenesis does not explain the intra-administration hyperthermic sign-reversal induced by serial administrations of 60% nitrous oxide to rats.

Al-Noori S, Ramsay D, Cimpan A, Maltzer Z, Zou J, Kaiyala K J Therm Biol. 2016; 60:195-203.

PMID: 27503733 PMC: 7266921. DOI: 10.1016/j.jtherbio.2016.07.018.

Persistence of a hyperthermic sign-reversal during nitrous oxide inhalation despite cue-exposure treatment with and without a drug-onset cue.

Kaiyala K, Woods S, Ramsay D Temperature (Austin). 2015; 1(3):268-275.

PMID: 25938128 PMC: 4416485. DOI: 10.4161/23328940.2014.944811.

Repeated nitrous oxide exposure in rats causes a thermoregulatory sign-reversal with concurrent activation of opposing thermoregulatory effectors.

Ramsay D, Woods S, Kaiyala K Temperature (Austin). 2015; 1(3):257-267.

PMID: 25938127 PMC: 4414259. DOI: 10.4161/23328940.2014.944809.

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