Conditioned place aversion and self-administration of nitrous oxide in rats

Ramsay, Douglas S.; Watson, Chae H.; Prall, Christopher W.; Kaiyala, Karl J.

doi:10.1016/s0091-3057(02)01048-1

Cited by 18 publications

(10 citation statements)

References 27 publications

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“…Squirrel monkeys will self-administered a combination of 60% N 2 O / 40% O 2 (Wood et al 1977). However, in a rat place conditioning and self-administration study, repeated pairings of an environment with 40 minute of exposures to 30% and 60% nitrous oxide produced a conditioned place aversion (Ramsay et al 2003) and inconsistent results in self-administration. Human self-administration and subjective tests of N 2 O exposure have been equally divergent among healthy subjects.…”

Section: Discussionmentioning

confidence: 99%

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

2013

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Rationale Despite widespread abuse there are few validated methods to study the rewarding effects of inhalants. One model that that may have utility for this purpose is intracranial self-stimulation (ICSS). Objectives We wished 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 1360-2900 ppm inhaled toluene vapor significantly facilitated ICSS in the rate frequency procedure and 1360 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. In 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.

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Section: Discussionmentioning

confidence: 99%

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

2013

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“…However, extending our present research paradigm to investigate the effect of individual differences in sensitivity and tolerance on drug consumption is hampered by the minimal work on N 2 O self-administration methods. N 2 O is a drug of abuse (Layzer 1985) and although self-administration methods exist for monkeys (Grubman and Woods 1982;Nemeth and Woods 1982;Wood et al 1977), there is only a single published study investigating N 2 O self-administration methods in the rat (Ramsay et al 2003). Finally, chronic tolerance development was evaluated over seven N 2 O exposure sessions.…”

Section: Discussionmentioning

confidence: 99%

Individual differences in initial sensitivity and acute tolerance predict patterns of chronic drug tolerance to nitrous-oxide-induced hypothermia in rats

2005

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Rationale: A preventive strategy for drug addiction would benefit from being able to identify vulnerable individuals. Understanding how an individual responds during an initial drug exposure may be useful for predicting how that individual will respond to repeated drug administrations.Objectives: This study investigated whether individual differences in initial drug sensitivity and acute tolerance can predict how chronic tolerance develops.Methods: During an initial 3-h administration of 60% nitrous oxide (N 2 O), male Long-Evans rats were screened for N 2 O's hypothermic effect into subsets based on being initially insensitive (II), sensitive with acute tolerance (AT), or sensitive with no intrasessional recovery (NR). Animals in each individual difference category were randomly assigned to receive six 90-min exposures of either 60% N 2 O or placebo gas. Core temperature was measured telemetrically.Results: Rats that exhibited a comparable degree of hypothermia during an initial N 2 O exposure, but differed in acute tolerance development, developed different patterns of chronic tolerance. Specifically, the NR group did not become fully tolerant over repeated N 2 O exposures while the AT group developed an initial hyperthermia followed by a return of core temperature to control levels indicative of full tolerance development. By the second N 2 O exposure, the II group breathing N 2 O became hyperthermic relative to the placebo control group and this hyperthermia persisted throughout the multiple N 2 O exposures.Conclusions: Individual differences in initial drug sensitivity and acute tolerance development predict different patterns of chronic tolerance. The hypothesis is suggested that individual differences in opponent adaptive responses may mediate this relationship.

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“…Additionally, the lack of significant metabolic pathways for N 2 O [ 15 ] limits pharmacokinetic factors from influencing the drug’s pharmacological effect during the initial drug challenge. Finally, N 2 O is an abused inhalant drug [ 16 ] and, like other drugs of abuse, N 2 O supports self-administration in animals [ 17 – 19 ], and it has positively reinforcing (rewarding) effects for humans [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Predicting Addictive Vulnerability: Individual Differences in Initial Responding to a Drug’s Pharmacological Effects

et al. 2015

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Considerable data suggest that individuals who appear minimally disrupted during an initial drug administration have elevated risk for abusing the drug later. A better understanding of this association could lead to more effective strategies for preventing and treating drug addiction. To investigate this phenomenon using a rigorous experimental model, we first administered the abused inhalant nitrous oxide (N2O) to rats in a total calorimetry and temperature system to identify groups that were sensitive or insensitive to the drug’s hypothermic effect. We then enrolled the two groups in a novel N2O self-administration paradigm. The initially insensitive rats self-administered significantly more N2O than sensitive rats, an important step in the transition to addiction. Continuous non-invasive measurement of core temperature and its underlying determinants during screening revealed that both groups had similarly increased heat loss during initial N2O administration, but that insensitive rats generated more heat and thereby remained relatively normothermic. Calorimetry testing conducted after self-administration revealed that whereas N2O’s effect on heat loss persisted comparably for both groups, initially insensitive rats actually over-responded by generating excess heat and becoming hyperthermic. Thus, rats with the greatest initial heat-producing compensatory response(s) appeared initially insensitive to N2O-induced hypothermia, subsequently self-administered more N2O, and developed hyperthermic overcompensation during N2O inhalation, consistent with increased abuse potential and an allostatic model of addictive vulnerability.

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Conditioned place aversion and self-administration of nitrous oxide in rats

Cited by 18 publications

References 27 publications

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

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

Individual differences in initial sensitivity and acute tolerance predict patterns of chronic drug tolerance to nitrous-oxide-induced hypothermia in rats

Predicting Addictive Vulnerability: Individual Differences in Initial Responding to a Drug’s Pharmacological Effects

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