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

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 (approximately 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 [(18)F]fluoroclebopride (FCP). Next, D(3) 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 D(3) receptor function in adults.

Fig. 1

Distribution volume ratios (DVRs) of [¹⁸F]FCP in control (open bars) and prenatally cocaine-exposed (shaded bars) monkeys in the caudate nucleus, putamen, and amygdala. Each bar represents mean±SEM values from ten monkeys

Fig. 2

Yawning induced by quinpirole (0.03–0.3 mg/kg) in female (a) and male (b) control (open bars) and prenatally cocaine-exposed (shaded bars) adult rhesus monkeys. c Represents mean data (male and female) for each group. Data are represented as the mean±SEM number of yawns in a 30-min observation period

Fig. 3

Relationship between peak number of yawns elicited by quinpirole and maximal cocaine dose received in utero (from Morris et al. 1996). Different symbols represent males (triangles) and females (circles)

Fig. 4

Effects of SKF 81297 on rate of eye blinking in control (a) and prenatally cocaine-exposed (b) male (filled bars) and female (open bars) monkeys. c Represents mean data (male and female) for each group. Each point represents mean±SEM values