Limits...
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

N2O Self-Administration Data for Initially Sensitive and Initially Insensitive Rats.Ternary diagram depicting the centered geometric mean proportions of time spent in each chamber for each of the eight 44-h dyads during N2O availability. The numbers 1–8 depicted in the figure represent the sequential order of self-administration dyads. Circled numbers represent dyads for initially insensitive rats (II, n = 16) while uncircled numbers represent dyads for the initially sensitive rats (IS, n = 16). The position of each point relative to the three color-coded axes indicates the proportion of time spent in the central tub (black), control gas chamber (red), and 60% N2O chamber (blue) during a 44-h dyad.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4400068&req=5

pone.0124740.g002: N2O Self-Administration Data for Initially Sensitive and Initially Insensitive Rats.Ternary diagram depicting the centered geometric mean proportions of time spent in each chamber for each of the eight 44-h dyads during N2O availability. The numbers 1–8 depicted in the figure represent the sequential order of self-administration dyads. Circled numbers represent dyads for initially insensitive rats (II, n = 16) while uncircled numbers represent dyads for the initially sensitive rats (IS, n = 16). The position of each point relative to the three color-coded axes indicates the proportion of time spent in the central tub (black), control gas chamber (red), and 60% N2O chamber (blue) during a 44-h dyad.

Mentions: The primary outcome variable for assessing N2O self-administration is based on the amount of time each rat spent in each of the three compartments of the self-administration apparatus (i.e., the side chamber containing 60% N2O, the control side chamber containing compressed air, and the central tub). As explained previously, since the total proportions of time spent in all three compartments must sum to unity, these data are considered compositional [25]. A standard method for representing the central tendency of compositional data is to use a centered geometric mean, which is rescaled so that its components sum to unity [26]. The centered geometric mean proportions of time that the two groups spent in each of the three compartments during the N2O self-administration phase are plotted for each dyad on a ternary diagram (Fig 2). The ternary diagram depicts the overall pattern of results, with the II group steadily increasing the time spent in the N2O chamber over dyads and the IS group exhibiting negligible proclivity to self-administer N2O. [The times each individual rat spent in each compartment type during each dyad are provided in S2, S3 Figs.]


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)

N2O Self-Administration Data for Initially Sensitive and Initially Insensitive Rats.Ternary diagram depicting the centered geometric mean proportions of time spent in each chamber for each of the eight 44-h dyads during N2O availability. The numbers 1–8 depicted in the figure represent the sequential order of self-administration dyads. Circled numbers represent dyads for initially insensitive rats (II, n = 16) while uncircled numbers represent dyads for the initially sensitive rats (IS, n = 16). The position of each point relative to the three color-coded axes indicates the proportion of time spent in the central tub (black), control gas chamber (red), and 60% N2O chamber (blue) during a 44-h dyad.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0124740.g002: N2O Self-Administration Data for Initially Sensitive and Initially Insensitive Rats.Ternary diagram depicting the centered geometric mean proportions of time spent in each chamber for each of the eight 44-h dyads during N2O availability. The numbers 1–8 depicted in the figure represent the sequential order of self-administration dyads. Circled numbers represent dyads for initially insensitive rats (II, n = 16) while uncircled numbers represent dyads for the initially sensitive rats (IS, n = 16). The position of each point relative to the three color-coded axes indicates the proportion of time spent in the central tub (black), control gas chamber (red), and 60% N2O chamber (blue) during a 44-h dyad.
Mentions: The primary outcome variable for assessing N2O self-administration is based on the amount of time each rat spent in each of the three compartments of the self-administration apparatus (i.e., the side chamber containing 60% N2O, the control side chamber containing compressed air, and the central tub). As explained previously, since the total proportions of time spent in all three compartments must sum to unity, these data are considered compositional [25]. A standard method for representing the central tendency of compositional data is to use a centered geometric mean, which is rescaled so that its components sum to unity [26]. The centered geometric mean proportions of time that the two groups spent in each of the three compartments during the N2O self-administration phase are plotted for each dyad on a ternary diagram (Fig 2). The ternary diagram depicts the overall pattern of results, with the II group steadily increasing the time spent in the N2O chamber over dyads and the IS group exhibiting negligible proclivity to self-administer N2O. [The times each individual rat spent in each compartment type during each dyad are provided in S2, S3 Figs.]

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