Voluntary inhalation of methamphetamine: a novel strategy for studying intake non-invasively
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The abuse of the psychostimulant methamphetamine (MA) is associated with substantial costs and limited treatment options. To understand the mechanisms that lead to abuse, animal models of voluntary drug intake are crucial.
We aimed to develop a protocol to study long-term non-invasive voluntary intake of MA in mice.
Mice were maintained in their home cages and allowed daily 1 h access to an attached tunnel leading to a test chamber in which nebulized MA was available. Restated, if they went to the nebulizing chamber, they self-administered MA by inhalation. This protocol was compared to injected and to imposed exposure to nebulized MA, in a series of seven experiments.
We established a concentration of nebulized MA at which motor activity increases following voluntary intake resembled that following MA injection and imposed inhalation. We found that mice regulated their exposure to MA, self-administering for shorter durations when concentrations of nebulized MA were increased. Mice acquire the available MA by repeatedly running in and out of the nebulizing chamber for brief bouts of intake. Such exposure to nebulized MA elevated plasma MA levels. There was limited evidence of sensitization of locomotor activity. Finally, blocking access to the wheel did not affect time spent in the nebulizing chamber.
We conclude that administration of MA by nebulization is an effective route of self-administration, and our new protocol represents a promising tool for examining the transitions from first intake to long-term use and its behavioral and neural consequences in a non-invasive protocol.
KeywordsAddiction Voluntary intake Self-administration Nasal administration Nebulization Non-invasive Sensitization
This study is supported by the Postdoctoral fellowship award from the Consejo Nacional de Ciencia y Tecnología (CONACYT) 186902 and CONACYT travel grants I010/152/2014 and C-133/2014 (C.J.P.), NSF grant 1256105 (RS), the American Physiological Society (APS) Summer Undergraduate Research Fellowship, the Barnard College Doris Schloss Rosenthal Internship (RS&MR), the Columbia University Summer Undergraduate Research Fellowship (RDK, MR, MT), the Barnard College Summer Research Internship (RDK, MT). We thank Dr. Shan Xie, PhD, of the Nathan Kline Research Institute Orangeburg NY for performing the MA assays.
Compliance with ethical standards
All experimental procedures were approved and conducted according to the Columbia University Institutional Animal Care and Use Committee.
Conflict of interest
The authors declare that they have no conflict of interest.
- Carroll ME, Meisch RA (1984) Increased drug-reinforced behavior due to food deprivation. In: Thompson T, Dews PB, Barrett JE (eds) Advances in behavioral pharmacology. Academic Press Inc., Orlando, FL, pp. 47–88Google Scholar
- Couper FJ, Logan BK (2004) Drugs and human performance fact sheets. In: Bureau WSPLS (ed). National Highway Traffic Safety Administration, Washington, DCGoogle Scholar
- Pittendrigh CS (1981) Circadian systems: entrainment. In: Aschoff J (ed) Biological rhythms. Springer US, New York, pp. 94–124Google Scholar
- SAMHSA (2014) National Survey on Drug Use and Health. Behavioral health trends in the United States: results from the 2014 National Survey on Drug Use and HealthGoogle Scholar
- United Nations Office on Drugs and Crime: World drug report (2011) http://www.unodc.org/documents/data-and-analysis/WDR2011/WDR2011-ExSumpdf
- Wheeler JM, Reed C, Burkhart-Kasch S, Li N, Cunningham CL, Janowsky A, Franken FH, Wiren KM, Hashimoto JG, Scibelli AC, Phillips TJ (2009) Genetically correlated effects of selective breeding for high and low methamphetamine consumption. Genes Brain Behav 8:758–771CrossRefPubMedPubMedCentralGoogle Scholar