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Predicting addictive vulnerability: individual differences in initial responding to a drug's pharmacological effects.

Ramsay DS, Al-Noori S, Shao J, Leroux BG, Woods SC, Kaiyala KJ - PLoS ONE (2015)

Bottom Line: 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.We then enrolled the two groups in a novel N2O self-administration paradigm.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral Health Sciences, University of Washington, Seattle, WA, United States of America.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Calorimetric Assessment During an Initial 60% N2O Administration Distinguishes Initially Sensitive from Initially Insensitive Rats.Thermal profiles ± pointwise SE (shaded areas) of rats designated as initially sensitive (IS, n = 16) and initially insensitive (II, n = 16) based upon a N2O screening test of n = 189 candidates. A: Core temperature (Tc); B: heat production (HP); C: dry heat loss (DHL), and D: evaporative heat loss (EHL). HP data between 0 and 12 min are not depicted because it has been documented that the initiation of N2O delivery can cause a transient artifactual effect on HP [14].
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pone.0124740.g001: Calorimetric Assessment During an Initial 60% N2O Administration Distinguishes Initially Sensitive from Initially Insensitive Rats.Thermal profiles ± pointwise SE (shaded areas) of rats designated as initially sensitive (IS, n = 16) and initially insensitive (II, n = 16) based upon a N2O screening test of n = 189 candidates. A: Core temperature (Tc); B: heat production (HP); C: dry heat loss (DHL), and D: evaporative heat loss (EHL). HP data between 0 and 12 min are not depicted because it has been documented that the initiation of N2O delivery can cause a transient artifactual effect on HP [14].

Mentions: Non-sibling adolescent male Long-Evans rats (n = 189) were exposed to 60% N2O for 3 h in a total calorimetry apparatus. Consistent with prior findings [23, 24], considerable inter-individual variability in the pattern of Tc was apparent. For each of the 8 squads screened (23–24 rats/squad), the 2 rats with the largest decrease of Tc and the 2 rats with the smallest decrease of Tc were selected for the self-administration phase of the study using previously described criteria [23, 24]. Therefore, the selection procedure yielded two groups of 16 rats each distinguished by the magnitude of the change in Tc during an initial exposure to 60% N2O (Fig 1A).


Predicting addictive vulnerability: individual differences in initial responding to a drug's pharmacological effects.

Ramsay DS, Al-Noori S, Shao J, Leroux BG, Woods SC, Kaiyala KJ - PLoS ONE (2015)

Calorimetric Assessment During an Initial 60% N2O Administration Distinguishes Initially Sensitive from Initially Insensitive Rats.Thermal profiles ± pointwise SE (shaded areas) of rats designated as initially sensitive (IS, n = 16) and initially insensitive (II, n = 16) based upon a N2O screening test of n = 189 candidates. A: Core temperature (Tc); B: heat production (HP); C: dry heat loss (DHL), and D: evaporative heat loss (EHL). HP data between 0 and 12 min are not depicted because it has been documented that the initiation of N2O delivery can cause a transient artifactual effect on HP [14].
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4400068&req=5

pone.0124740.g001: Calorimetric Assessment During an Initial 60% N2O Administration Distinguishes Initially Sensitive from Initially Insensitive Rats.Thermal profiles ± pointwise SE (shaded areas) of rats designated as initially sensitive (IS, n = 16) and initially insensitive (II, n = 16) based upon a N2O screening test of n = 189 candidates. A: Core temperature (Tc); B: heat production (HP); C: dry heat loss (DHL), and D: evaporative heat loss (EHL). HP data between 0 and 12 min are not depicted because it has been documented that the initiation of N2O delivery can cause a transient artifactual effect on HP [14].
Mentions: Non-sibling adolescent male Long-Evans rats (n = 189) were exposed to 60% N2O for 3 h in a total calorimetry apparatus. Consistent with prior findings [23, 24], considerable inter-individual variability in the pattern of Tc was apparent. For each of the 8 squads screened (23–24 rats/squad), the 2 rats with the largest decrease of Tc and the 2 rats with the smallest decrease of Tc were selected for the self-administration phase of the study using previously described criteria [23, 24]. Therefore, the selection procedure yielded two groups of 16 rats each distinguished by the magnitude of the change in Tc during an initial exposure to 60% N2O (Fig 1A).

Bottom Line: 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.We then enrolled the two groups in a novel N2O self-administration paradigm.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral Health Sciences, University of Washington, Seattle, WA, United States of America.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus