Primates exposed to cocaine in utero display reduced density and number of cerebral cortical neurons

Abstract

This study examined the effects of cocaine use during the second trimester of pregnancy on cerebral neocortical volume and density, and total number of neocortical neurons and glia in offspring. We also evaluated the extent of postnatal recovery of cytoarchitectural abnormalities previously observed in the neocortex of two-month-old primates born from cocaine-treated mothers (Lidow [1995] Synapse 21:332-334). Pregnant monkeys received cocaine orally (20 mg/kg/day) from the 40th to 102nd days of pregnancy (embryonic day [E]40-E102). On E64 and E65, the animals were injected with [(3)H]thymidine. Cerebral hemispheres of the offspring were examined at three years of age. We found a reduction in the neocortical volume and density and total number of neocortical neurons. The observed reduction in neuronal number within the neocortex was not accounted for by the increase in the number of neurons in the white matter of cocaine-exposed animals, because the number of these "extra" neurons was equal to only half that of missing neurons. We detected no significant changes in the number of neocortical glia. The cytoarchitectural abnormalities in the neocortex of prenatally cocaine-exposed three-year-old monkeys closely resembled previously described neocortical abnormalities in similarly exposed two-month-old animals: the neocortex lacked a discernible lamination; the majority of the cells labeled by [(3)H]thymidine injected during neocortical neurogenesis did not reach their proper position within the cortical plate. Therefore, postnatal maturation is not associated with significant improvement in neocortical organization in primates prenatally exposed to cocaine. There was, however, a postnatal recovery of low glial fibrillary acidic protein (GFAP) immunoreactivity previously observed in 2-month-old cocaine-exposed animals.

Computational models of ethanol‐induced neurodevelopmental toxicity across species: Implications for risk assessment

“…For example, in primate species neurogenesis lasts 10-14 times longer than in rodents (6 and 7 days in the mouse and rat compared to 60 and 84 days in the rhesus monkey and human) (Rakic and Kornack, 2001). In addition, the cell cycle length is approximately twice as long in the rhesus monkey compared with the mouse or rat (Kornack and Rakic, 1998;Nowakowski et al, 1989;Takahashi et al, 1995), and the monkey and human neocortices are estimated to contain over 400 and 1,000 times as many neurons as the rat neocortex, respectively (Duffell et al, 2000;Lidow and Song, 2001;Pakkenberg and Gundersen, 1997).…”

Clinical Implications of Cocaine-Induced Cortical Depression

“…The authors previously reported similar findings after repeated cocaine administration, and should be commended for their pursuit of cocaine-induced neuroadaptations through in vivo single-cell recording studies. In other animal studies, chronic exposure to cocaine also produces dysfunctional morphological changes (Robinson et al, 2001) and reduced numbers (Lidow and Song, 2001) of PFC pyramidal neurons, which is consistent with reports (reviewed elsewhere) that cocaine-dependent patients have reductions in PFC metabolism and gray matter density, and perform poorly on standardized tests that assess frontal function (Dackis and O'Brien, 2003). While the authors reasonably concluded that electrophysiological alterations of pyramidal neurons might affect attention, working memory, and information processing, we believe that PFC dysfunction may also be a core component of cocaine addiction, and contribute to many baffling characteristics of addicted patients that were once thought to be purely psychological.…”

Effects of Psychostimulant Drugs on Developing Brain

“…On yıllardır yapılan preklinik araştırma-lar bu etkilerin ifade buluşunun geciktiğini ve erişkinlikte ortaya çıktığını göstermektedir. [30][31][32][33] İlacın etkileri, bir nevi kuluçkaya yatmaktadır. Bu kavram "nöronal imprinting" olarak adlandırılmaktadır.…”

“…[30][31][32][33] İmprinting, nöronların toksik hasarlanmasına yol açmamakta, ancak duyarlı zaman dilimlerinde ardı-şık olarak ilaçla karşılaşma durumunda duyarlılığa etki etmektedir. [31][32][33][34] Hedef sistemin olgunlaşma durumu ilaca maruziyetin uzun dönem etkilerini belirlemede önemlidir. [32,33] Temel psikiyatrik bozukluklar için, tedavi edici işlev monoaminerjik sistemler yoluyla olmaktadır.…”

“…[31][32][33][34] Hedef sistemin olgunlaşma durumu ilaca maruziyetin uzun dönem etkilerini belirlemede önemlidir. [32,33] Temel psikiyatrik bozukluklar için, tedavi edici işlev monoaminerjik sistemler yoluyla olmaktadır. Bu sistem ergenlik ile genç erişkinlik arasında olgun hale gelmektedir.…”