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Voluntary inhalation of methamphetamine: a novel strategy for studying intake non-invasively

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Abstract

Rationale

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.

Objectives

We aimed to develop a protocol to study long-term non-invasive voluntary intake of MA in mice.

Methods

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.

Results

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.

Conclusions

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.

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Acknowledgements

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.

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Authors and Affiliations

  1. Centro de Investigaciones Biomédicas, Universidad Veracruzana, Veracruz, Mexico

    C. Juarez-Portilla

  2. Neuroscience Program and Department of Psychology, Barnard College of Columbia University, New York, NY, 10027, USA

    R. D. Kim, M. Robotham, M. Tariq, M. Pitter, J. LeSauter & R. Silver

  3. Department of Psychology, Columbia University, New York, NY, 10027, USA

    C. Juarez-Portilla, J. LeSauter & R. Silver

  4. Department of Pathology and Cell Biology, Columbia University Health Sciences, New York, 10032, NY, USA

    R. Silver

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  1. C. Juarez-Portilla
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  2. R. D. Kim
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Correspondence to R. Silver.

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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.

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Juarez-Portilla, C., Kim, R.D., Robotham, M. et al. Voluntary inhalation of methamphetamine: a novel strategy for studying intake non-invasively. Psychopharmacology 234, 739–747 (2017). https://doi.org/10.1007/s00213-016-4510-8

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  • DOI: https://doi.org/10.1007/s00213-016-4510-8

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