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Age-dependent changes in cocaine sensitivity across early ontogeny in male and female rats: possible role of dorsal striatal D2High receptors

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Abstract

Rationale

Responsiveness to acute psychostimulant administration varies across ontogeny.

Objective

The purpose of the present study was to determine if age-dependent changes in D2High receptors may be responsible for the ontogeny of cocaine sensitivity in preweanling, adolescent, and adult rats.

Methods

[3H]-Domperidone/dopamine competition assays were used to determine ontogenetic changes in the proportion of D2High receptors in male and female preweanling [postnatal day (PD) 5, 10, 15, and 20], adolescent (PD 40), and adult (PD 80) rats. In the behavioral experiment, responsiveness to cocaine (2.5, 5, 10, or 20 mg/kg) was assessed on PD 20, PD 40, and PD 80 for 60 min. Male and female rats were habituated to the apparatus on the 2 days prior to testing. Distance traveled data were presented both untransformed and as percent of saline controls.

Results

Male and female preweanling rats (PD 5–PD 20) had a significantly greater percentage of dorsal striatal D2High receptors than adolescent or adult rats. Likewise, preweanling rats (PD 20) were more sensitive to the behavioral effects of cocaine than the two older age groups. Adolescent and adult rats responded in a generally similar manner; however, analysis of the untransformed locomotor activity data suggested that adolescent rats were hyporesponsive to 2.5 and 20 mg/kg cocaine when compared to adults.

Conclusions

Data from the present study are consistent with the hypothesis that ontogenetic changes in D2High receptors are responsible for age-dependent differences in psychostimulant sensitivity.

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This research was supported by NIMH research grant MH102930 (SAM).

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All authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Psychology, California State University, 5500 University Parkway, San Bernardino, CA, 92407, USA

    Sanders A. McDougall, Shannon E. Eaton, Alena Mohd-Yusof & Cynthia A. Crawford

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  1. Sanders A. McDougall
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  2. Shannon E. Eaton
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  3. Alena Mohd-Yusof
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  4. Cynthia A. Crawford
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Correspondence to Sanders A. McDougall.

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McDougall, S.A., Eaton, S.E., Mohd-Yusof, A. et al. Age-dependent changes in cocaine sensitivity across early ontogeny in male and female rats: possible role of dorsal striatal D2High receptors. Psychopharmacology 232, 2287–2301 (2015). https://doi.org/10.1007/s00213-014-3860-3

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  • DOI: https://doi.org/10.1007/s00213-014-3860-3

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