Cocaine-induced alterations in the density of monoaminergic receptors in the embryonic guinea pig cerebral wall

Abstract

Quantitative receptor autoradiography was used to examine the effect of chronic cocaine exposure on the density of alpha1-, alpha2- and beta-adrenergic, 5-HT1A- and 5-HT2-serotonergic, and D1- and D2-dopaminergic receptors in the fetal guinea pig cerebral wall which contained forming motor area of the cerebral cortex. The pregnant guinea pig received two daily subcutaneous injections of 20 mg/kg cocaine beginning on the 20th day of pregnancy (E20). The control animals received injections of equivalent volume of saline. The receptor densities were examined between days 5-30 of the treatment, which corresponds to E25-E50. By the fifth day of treatment (E25), cocaine produced downregulation of all receptors studied throughout the entire depth of the fetal cerebral wall. More extended treatment, however, resulted in recovery of receptor levels. Finally, from days 20-30 of treatment (E40-E50) there was a significant upregulation of noradrenergic and dopaminergic receptor sites. These findings demonstrate that exposure to cocaine in utero can influence adrenergic, serotonergic, and dopaminergic receptors in the embryonic cerebral wall, which may lead to alteration in corticogenesis. Furthermore, the present study reveals that, in the course of chronic treatment, cocaine may completely reverse its receptor regulatory activity in the fetal brain.

Cocaine‐induced inhibition of process outgrowth in locus coeruleus neurons: role of gestational exposure period and offspring sex

“…The presence of significant alterations from partial gestational exposure, in the absence of any significant alterations from the combined, more typical preclinical study commonplace in the literature is not as puzzling as it may initially appear. Lidow and colleagues (Lidow et al, 1999) reported a similar profile of effects, early gestational cocaine exposure initially resulted in receptor down-regulation for adrenergic, dopaminergic and serotonergic systems, but extended treatment resulted in recovery of receptor levels (Lidow et al, 1999). The relative scarcity of reported effects of prenatal cocaine exposure on the noradrenergic system may indeed be a reflection of the use of exposure protocols that mask the very effect they seek to detect.…”

Cocaine induces cell death within the primate fetal cerebral wall

“…The third and final mechanism that may be involved in in utero cocaine‐induced cell death is based on the well‐known monoamine uptake–blocking properties of cocaine, which results in an elevation of the intracellular levels of monoaminergic neurotransmitters such as dopamine, noradrenaline, adrenaline and serotonin [reviewed in 15]. The normal fetal cerebrum contains defined levels of monoaminergic neurotransmitters [ 20, 27] that are released there by specific afferents as well as arriving by diffusion from the circulation through an as yet undeveloped blood–brain barrier [reviewed in 20, 24]. These neurotransmitters play important roles in the regulation of the proliferation, migration and differentiation of cerebral cortical cells [ 23, 38, 51, 52].…”

D1 dopamine receptor regulation of cell cycle in FGF‐ and EGF‐supported primary cultures of embryonic cerebral cortical precursor cells

“…Several reports have revealed that cells of the germinative zones of the fetal cerebral wall express high levels of D1 dopamine receptors (D1Rs; Schambra et al, 1994;Lidow, 1995;Lidow and Rakic, 1995;Lidow et al, 1999;Reinoso et al, 1996;Wang et al, 1997) and their milieu may contain dopamine at concentrations comparable to those in the adult cerebral cortex (Masudi and Gilmore, 1983;Lidow, 1998). While the ability of D1Rs to influence proliferation has been demonstrated in lymphocytes, meningioma, and vascular smooth muscle cells (Schrell et al, 1990;Yasunari et al, 1997;Saha et al, 2001), the possible role of these receptors in the regulation of cell division during corticogenesis has not been investigated.…”