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Behavioral effects of dopamine receptor inactivation during the adolescent period: age-dependent changes in dorsal striatal D2High receptors

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Abstract

Rationale

Dopamine (DA) receptor inactivation produces opposing behavioral effects across ontogeny. For example, inactivating DA receptors in the dorsal striatum attenuates DA agonist-induced behaviors of adult rats, while potentiating the locomotor activity of preweanling rats.

Objective

The purpose of this study was to determine if DA receptor inactivation potentiates the DA agonist-induced locomotor activity of adolescent rats and whether alterations in D2High receptors are responsible for this effect.

Methods

In the behavioral experiment, the irreversible receptor antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) or its vehicle (100 % dimethyl sulfoxide, DMSO) was bilaterally infused into the dorsal striatum on postnatal day (PD) 39. On PD 40, adolescent rats were given intrastriatal infusions of the DA agonist R(−)-propylnorapomorphine (NPA) or vehicle and locomotor activity was measured for 40 min. In the receptor binding experiment, rats received IP injections of EEDQ or DMSO (1:1 (v/v) in distilled water) on PD 17, PD 39, or PD 84. One day later, striatal samples were taken and subsequently assayed for D2-specific binding and D2High receptors using [3H]-domperidone.

Results

Unlike what is observed during the preweanling period, EEDQ attenuated the NPA-induced locomotor activity of adolescent rats. EEDQ reduced D2 receptor levels in the dorsal striatum of all age groups while increasing the proportion of D2High receptors. Regardless of pretreatment condition (i.e., DMSO or EEDQ), preweanling rats had a greater percentage of D2High receptors than adolescent or adult rats.

Conclusions

DA receptor inactivation affects the behaviors of preweanling and older rats differently. The DA supersensitivity exhibited by EEDQ-treated preweanling rats may result from an excess of D2High receptors.

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Acknowledgments

This research was supported by NIMH research grant MH102930 (SAM) and NIGMS training grant GM083883 (AEG).

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All authors declare no conflict of interest.

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

    Sanders A. McDougall, Joseph M. Valentine, Ashley E. Gonzalez, Danielle E. Humphrey, Crystal B. Widarma & Cynthia A. Crawford

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  1. Sanders A. McDougall
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  2. Joseph M. Valentine
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  3. Ashley E. Gonzalez
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  4. Danielle E. Humphrey
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  5. Crystal B. Widarma
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Correspondence to Sanders A. McDougall.

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McDougall, S.A., Valentine, J.M., Gonzalez, A.E. et al. Behavioral effects of dopamine receptor inactivation during the adolescent period: age-dependent changes in dorsal striatal D2High receptors. Psychopharmacology 231, 1637–1647 (2014). https://doi.org/10.1007/s00213-013-3355-7

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