Prenatal cocaine exposure alters alpha2 receptor expression in adolescent rats - PubMed (original) (raw)

Prenatal cocaine exposure alters alpha2 receptor expression in adolescent rats

Rosemarie M Booze et al. BMC Neurosci. 2006.

Abstract

Background: Prenatal cocaine exposure produces attentional deficits which to persist through early childhood. Given the role of norepinephrine (NE) in attentional processes, we examined the forebrain NE systems from prenatal cocaine exposed rats. Cocaine was administered during pregnancy via the clinically relevant intravenous route of administration. Specifically, we measured alpha2-adrenergic receptor (alpha2-AR) density in adolescent (35-days-old) rats, using [3H]RX821002 (5 nM).

Results: Sex-specific alterations of alpha2-AR were found in the hippocampus and amygdala of the cocaine-exposed animals, as well as an upregulation of alpha2-AR in parietal cortex.

Conclusion: These data suggest that prenatal cocaine exposure results in a persistent alteration in forebrain NE systems as indicated by alterations in receptor density. These neurochemical changes may underlie behavioral abnormalities observed in offspring attentional processes following prenatal exposure to cocaine.

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Figures

Figure 1

Representative competition ("cold saturation") analysis curve measured in hippocampus from male and female offspring exposed to cocaine in utero. Analysis was performed by the addition of 2 nM [3H] RX821002 added to tubes containing unlabeled RX821002 (1 pM – 1μM) or 10μM phentolamine (nonspecific binding). Data were best fit to a single-site model with hill slopes (nH) approaching unity. Calculated Kd and BMAX values are expressed in Table 1.

Figure 2

Representative false-color (RGB) autoradiograms of [3H]RX821002 binding density in brain slices from adolescent males and females exposed to either saline or cocaine in utero. Areas of low binding density appear white to light purple, areas of moderate binding appear blue to yellow, and areas of high binding density appear dark red. Measurements were taken from hippocampus (stratum lacunosum-moleculare of CA1 near the hippocampal fissure, as approximately marked by a red oval), parietal cortex (layer II, as approximately marked by an orange rectangle), and amygdala (central nucleus, as approximately marked by a blue square).

Figure 3

Density of α2-adrenergic receptors in laconosum-moleculare layer of hippocampal area CA1 as measured by autoradiography. Data are expressed as mean density (± S.E.M.). In control animals prenatally exposed to saline, the density of hippocampal CA1 α2-adrenergic receptors in male rats was significantly [F(1, 52) = 23.2; P < 0.0001] lower than the density of α2-adrenergic receptors observed in female controls. Prenatal cocaine exposure abolished this sex difference in hippocampal α2-adrenergic receptors by increasing binding 21% in male offspring, whereas α2-adrenergic receptors did not significantly differ by drug exposure in females. n = 14 per group.

Figure 4

Density of α2 adrenergic receptors in parietal cortex (layer II) as measured by autoradiography. Data are expressed as mean density (± S.E.M.). In the parietal cortex, prenatal cocaine exposure increased α2 adrenergic receptors in both sexes [F(1, 52) = 4.1; P < 0.05]. n = 14 per group.

Figure 5

Density of α2-adrenergic receptors in amygdala (central nucleus) as measured by autoradiography. In control animals, the density of α2-adrenergic receptors was significantly lower [F(1, 52) = 10.9; P < 0.01] in females than the density of α2-adrenergic receptors observed in male controls. Prenatal cocaine exposure abolished this sex difference in amygdala α2-adrenergic receptors by increasing binding by 19% in female offspring, whereas α2-adrenergic receptors did not significantly differ because of cocaine exposure in males. n = 14 per group.

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Prenatal cocaine exposure alters alpha2 receptor expression in adolescent rats - PubMed (original) (raw)