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Importance of D1 receptors for associative components of amphetamine-induced behavioral sensitization and conditioned activity: a study using D1 receptor knockout mice

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Abstract

Rationale

Repeated exposure to psychostimulant drugs results in conditioned activity and behavioral sensitization. Nonassociative cellular changes are necessary for behavioral sensitization, while associative processes appear to modify the sensitized response.

Objective

The purpose of the present study was to determine whether the absence of the D1 receptor would disrupt associative processes modulating sensitization and conditioned activity.

Methods

Wild-type and D1 receptor knockout mice (i.e., D1-deficient mice) were injected with amphetamine (AMPH; 8 mg/kg, IP) before being placed in a previously novel test chamber (AMPH-Test group) or before being returned to the home cage (AMPH-Home group). Separate groups of mice were injected with saline (SAL) at the same time points. Distance traveled was measured 60 min each day, with the preexposure phase lasting 1 or 7 days. Sensitization was subsequently assessed after an injection of AMPH (1 mg/kg, IP), while conditioned activity was assessed after an injection of SAL.

Results

After a 1-day preexposure phase, wild-type and D1-deficient mice exhibited similar patterns of sensitization and conditioned activity. After a 7-day preexposure phase, (1) D1-deficient mice exhibited more robust context-specific sensitization than wild-type mice, (2) only D1-deficient mice showed context-independent sensitization, and (3) only D1-deficient mice showed conditioned activity.

Conclusions

Repeatedly treating D1-deficient mice with AMPH appears to cause a general increase in responsivity. The reason for this hyper-responsivity is uncertain, but it is possible that cues from the testing environment were unable to inhibit responding (i.e., associative processes were disrupted). Alternatively, compensatory mechanisms (e.g., increases in D2-like receptors) may affect processes underlying sensitization and conditioned activity.

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Acknowledgements

We thank Eva Newman for help with testing the animals. This work was partially supported by a grant from the National Institutes of Health (DA12169) to C.A.C. and an ASI research grant (CSUSB) to P.E.K.

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  1. Carmela M. Reichel

    Present address: Department of Psychology, University of Nebraska-Lincoln, 238 Burnett Hall, Lincoln, NE, 68588, USA

  2. Arbi Nazarian

    Present address: Department of Anesthesiology, University of California, 9500 Gilman Drive, La Jolla, San Diego, CA, 92093, USA

Authors and Affiliations

  1. Department of Psychology, California State University, San Bernardino, CA, 92407, USA

    Sanders A. McDougall, Carmela M. Reichel, Michelle C. Cyr, Patrick E. Karper, Arbi Nazarian & Cynthia A. Crawford

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  1. Sanders A. McDougall
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  2. Carmela M. Reichel
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Correspondence to Sanders A. McDougall.

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McDougall, S.A., Reichel, C.M., Cyr, M.C. et al. Importance of D1 receptors for associative components of amphetamine-induced behavioral sensitization and conditioned activity: a study using D1 receptor knockout mice. Psychopharmacology 183, 20–30 (2005). https://doi.org/10.1007/s00213-005-0146-9

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