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Behavioral inhibition in mice bred for high vs. low levels of methamphetamine consumption or sensitization

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Abstract

Rationale

Research indicates that genetics influence methamphetamine self-administration as well as sensitization to the psychomotor-stimulating effects of methamphetamine (MA). Other studies have suggested that heightened levels of impulsivity, including low levels of behavioral inhibition, are associated with the use of drugs, including MA.

Objectives

The current study examined whether lines of mice selected for traits associated with a heightened risk of developing MA dependence would also exhibit low levels of drug-naïve inhibition and whether administration of MA would result in different levels of inhibition in animals selected to consume or respond more to MA.

Methods

A go/no-go task was used to assess inhibition in male and female mice selected for low or high levels of MA consumption or selected for high or low levels of locomotor sensitization to repeated injections of MA.

Results

Mice selected for MA sensitization differed in false alarms, precue response rates (measures of behavioral inhibition), and also hits (measure of operant responding). Mice selected for MA consumption did not differ in measures of behavioral inhibition, though hits differed. When MA was administered prior to the task, false alarms, precue response rates, and hits decreased for mice from all selected lines. Female high drinking mice were particularly resistant to MA’s effects on hits, but not precue response rate or false alarms.

Conclusions

These data suggest a shared, but complex, genetic association between inhibition processes, general levels of operant responding, and MA sensitization or consumption.

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Acknowledgments

SHM and TJP designed the study, TMM and KAS collected the data with help from Noah Gubner and Ryan McLaughlin, data analysis was performed by TMM, KAS and SHM, all authors were involved in data interpretation and manuscript preparation. This research was supported by the Methamphetamine Abuse Research Center (P50 DA018165), the Department of Veterans Affairs, and the Portland Alcohol Research Center (P60 AA10760). TMM was supported by NIAAA T32 training grant AA007468. All research was conducted in compliance with laws in USA.

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Authors and Affiliations

  1. Department of Behavioral Neuroscience L470, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA

    Travis M. Moschak, Katherine A. Stang, Tamara J. Phillips & Suzanne H. Mitchell

  2. Department of Psychiatry, Oregon Health & Science University, Portland, OR, USA

    Suzanne H. Mitchell

  3. Methamphetamine Abuse Research Center, Oregon Health & Science University, Portland, OR, USA

    Tamara J. Phillips & Suzanne H. Mitchell

  4. Portland Veterans Affairs Medical Center, Portland, OR, USA

    Tamara J. Phillips

Authors
  1. Travis M. Moschak
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  2. Katherine A. Stang
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  4. Suzanne H. Mitchell
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Correspondence to Suzanne H. Mitchell.

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Moschak, T.M., Stang, K.A., Phillips, T.J. et al. Behavioral inhibition in mice bred for high vs. low levels of methamphetamine consumption or sensitization. Psychopharmacology 222, 353–365 (2012). https://doi.org/10.1007/s00213-012-2650-z

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  • DOI: https://doi.org/10.1007/s00213-012-2650-z

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