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The missing variable: ultrasonic vocalizations reveal hidden sensitization and tolerance-like effects during long-term cocaine administration

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Abstract

Rationale

Subtypes of 50-kHz ultrasonic vocalizations (USVs) in rats are thought to reflect positive affect and occur with cocaine or amphetamine delivery. In contexts predicting forthcoming cocaine, pre-drug anticipatory USVs are initially minimal during daily sessions but gradually escalate over several weeks, presumably as the animal learns to expect and look forward to impending drug access. To gain more insight into motivational aspects of cocaine intake in animal models of drug dependence studies, it is important to compare experience-dependent changes in lever response rate, USVs, and locomotion during cocaine conditioning and extinction trials.

Objective

To address whether cocaine-induced increases in lever responding and locomotor activity correspond with USV production. The study also determined whether short-term cocaine and context deprivation effects could be detected during conditioning or extinction.

Methods

Rats underwent 20 days of 60-min sessions of self- or yoked administration of cocaine (0.75 mg/kg/infusion, i.v.), followed by 19 days of extinction training (8 weeks total, weekends off).

Results

Lever responding for cocaine and cocaine-induced locomotor activity increased across conditioning sessions. In contrast, the number of frequency modulated 50-kHz USVs evoked in response to cocaine infusion decreased with cocaine experience, suggesting perhaps tolerance to the rewarding properties of the drug. In addition, USVs but not lever pressing or locomotion are affected after brief periods of drug and/or drug context abstinence.

Conclusions

Except for initial drug exposure, increased cocaine seeking during cocaine delivery could reflect either enhanced drug motivation or the development of drug tolerance, but not enhanced positive affect.

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Acknowledgments

We thank Sean Ma for his technical support in USV recording and analysis; Todd Maddox for his assistance in USV data analyses; Leah McAleer and Neha Thakore for their assistance with technical and personnel management; and Tiffany Nguyen, John Jiles, Sam Ryo, Hunter Owen, Donna Chan, Ernest Tong, Suk Hyun Lee,Tian Tian, Linda Ju, Rachel Chavana, Rosie Maddox, Amarachi Amuneke, Ellen Kusey, and Michael Rotko for their help with USV data organization and assessment.

Funding

This work was supported by NIH grants DA014640 and DA014640-05S1, the University of Texas VP Research Office (C.L.D.), NIDA Drug Supply Program, the Davis Phinney Foundation (T.S.), and the University of Texas Waggoner Center for Alcohol and Addiction Research Bruce-Jones Graduate Fellowship (E.Y.M., A.M.A.).

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Authors and Affiliations

  1. Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas, Austin, TX, 78712, USA

    Esther Y. Maier & Christine L. Duvauchelle

  2. Department of Biology, University of Texas, Austin, TX, 78712, USA

    Mohamed Abdalla

  3. Department of Psychology and Institute for Neuroscience, University of Texas, Austin, TX, 78712, USA

    Allison M. Ahrens & Timothy Schallert

  4. PHAR-Pharmacology, University of Texas, 1 University Station A1915, Austin, TX, 78712-0125, USA

    Christine L. Duvauchelle

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  1. Esther Y. Maier
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  2. Mohamed Abdalla
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  3. Allison M. Ahrens
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  4. Timothy Schallert
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  5. Christine L. Duvauchelle
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Corresponding author

Correspondence to Christine L. Duvauchelle.

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Maier, E.Y., Abdalla, M., Ahrens, A.M. et al. The missing variable: ultrasonic vocalizations reveal hidden sensitization and tolerance-like effects during long-term cocaine administration. Psychopharmacology 219, 1141–1152 (2012). https://doi.org/10.1007/s00213-011-2445-7

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  • DOI: https://doi.org/10.1007/s00213-011-2445-7

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