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Characterization of the dopamine receptor system in adult rhesus monkeys exposed to cocaine throughout gestation

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Abstract

Rationale

Cocaine use during pregnancy is associated with alterations in the dopamine (DA) system in the fetal brain. However, little is known about the effects of prenatal cocaine exposure on the postnatal dopaminergic system.

Objectives

The objective of the study was to examine DA receptor function in adult monkeys that were prenatally exposed to cocaine.

Materials and methods

Male and female rhesus monkeys (∼13 years old) that had been prenatally exposed to cocaine (n = 10) and controls (n = 10) were used in all studies. First, DA D2-like receptor availability was assessed using positron emission tomography and the D2-like receptor radiotracer [18F]fluoroclebopride (FCP). Next, D3 receptor function was assessed by measuring quinpirole-induced yawning (0.03–0.3 mg/kg). Finally, D1-like receptor function was examined by measuring eye blinking elicited by the high-efficacy D1-like receptor agonist SKF81297 (0.3–3.0 mg/kg).

Results

There were no differences between groups or sexes in D2-like receptor availability in the caudate nucleus, putamen or amygdala. However, quinpirole elicited significantly more yawns in prenatally cocaine-exposed monkeys compared with control monkeys. A significant correlation between gestational dose of cocaine and peak effects of quinpirole was observed. In all monkeys, administration of SKF81297 elicited dose-dependent increases in eye blinks that did not differ between groups.

Conclusions

These findings suggest that prenatal cocaine exposure can have long-term effects on DA D3 receptor function in adults.

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Acknowledgements

This research was supported by National Institute on Drug Abuse grants R01 DA25120, R37 DA10584 and K31 DA024485. The authors report no conflict of interest and would like to acknowledge the technical assistance of Tonya Calhoun, Kimberly Black, Holly Smith, and Whitney Wilson. The authors also thank Dr. Merle Paule for providing information related to the histories of these monkeys and Dr. Anthony Liguori for statistical consultation.

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, Wake Forest University School of Medicine, 546 NRC, Medical Center Blvd., Winston-Salem, NC, 27157-1083, USA

    Lindsey R. Hamilton, Paul W. Czoty & Michael A. Nader

  2. Department of Radiology, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    H. Donald Gage & Michael A. Nader

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  1. Lindsey R. Hamilton
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  2. Paul W. Czoty
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  3. H. Donald Gage
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  4. Michael A. Nader
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Correspondence to Michael A. Nader.

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Hamilton, L.R., Czoty, P.W., Gage, H.D. et al. Characterization of the dopamine receptor system in adult rhesus monkeys exposed to cocaine throughout gestation. Psychopharmacology 210, 481–488 (2010). https://doi.org/10.1007/s00213-010-1847-2

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  • DOI: https://doi.org/10.1007/s00213-010-1847-2

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