Male Rats Exposed to Cocaine in utero Demonstrate Elevated Expression of Fos in the Prefrontal Cortex in Response to Environment

Abstract

Prenatal cocaine exposure has been associated with disruption in attention and short-term memory in exposed children and in animal models. The biochemical change or changes responsible for these cognitive deficits are not known. An intriguing possibility, however, is that cocaine exposure during development disrupts the morphology or function of the frontal cortex, a region thought to contribute to cognitive and executive functions. In this report, we examined the effects of intravenous prenatal cocaineThe abuse of cocaine during pregnancy has not been associated with major anatomical birth defects; however, a significant numbers of children exposed to cocaine in utero go on to develop select cognitive deficits, such as memory deficits, impulsivity, and difficulties in modulating attention (Delaney-Black et al. 1998; DowEdwards et al. 1999). Behavioral studies in animal models of prenatal cocaine exposure have demonstrated similar deficits in memory (Choi et al. 1998a;Cutler et al. 1996;Heyser et al. 1995;Levin and Seidler 1993;Morrow et al. 2000b;Tonkiss et al. 1997;Vorhees et al. 1995) and attention (Garavan et al. 2000;Mactutus 1999;Romano and Harvey 1996). The identification of the sites and the underlying biochemical changes induced by in utero exposure to cocaine, however, remain elusive. Understanding the biochemical substrates of the behavioral deficits induced by prenatal cocaine is necessary if logical treatments for the condition are to be developed. We have chosen to use the expression of the immediateearly gene, c-fos , as a marker of neuronal activation. NO . 3 Many researchers, including in our own laboratory, have successfully used this marker to map and study stress responses (Kovacs 1998). The expression of Fos, however, does not solely indicate that the neuron has been activated but indicates that the neuron is in the process of undergoing longer-term adaptation brought about by activation.One potential candidate site for the cognitive effects of prenatal cocaine is the frontal cortex. Dysfunction in this region has been associated with disruption in cognitive processes, including memory and attention (Goldman-Rakic 1998). Additionally, deficits in shortterm working memory can be observed with altered dopaminergic function in the prefrontal cortex of rats and non-human primates (Goldman-Rakic 1998;Morrow et al. 2000c;Murphy et al. 1996). One obvious mechanism by which prenatal cocaine exposure could impact on the frontal cortex is by blockade by cocaine of the monoamine transporters, including that of dopamine, in that region. Fetal changes in monoamine levels in the developing frontal cortex could potentially result in an anatomical or functional disruption (Levitt 1998;Pendleton et al. 1998). Wang and colleagues reported changes in the GABAergic neurons in the cortex, leading to the hypothesis that prenatal cocaine exposure could result in a disruption of the excitatory/inhibitory balance (Wang et al. 1995(Wang et al. , 1996. In this current report, we investigate potential changes in th...

The effects of prenatal cocaine use on infant development

“…This hypothesis has also been supported in animal studies [1,8,15,30,63,67,85,86,92,94]. The prefrontal cortex is one site that is thought to control arousal, attention, and mood, as well as executive functioning (the ability to plan and carry out actions) [17,23].…”

The effects of prenatal cocaine, post-weaning housing and sex on conditioned place preference in adolescent rats

“…Testing without the drug may render the drug-associated context more novel than the saline context on the test day (see Bardo & Bevins 2000 for additional discussion). Since prenatal cocaine has been reported to alter responses to novelty (Morrow et al 2002), one cannot exclude the possibility that differential responses to the novel aspects of the drug-paired chamber contributed to the results obtained.…”

Effects of Prenatal Cocaine Exposure on Social Development in Mice

“…These results might also suggest less inhibition and an increased likelihood of risktaking behavior in adolescent mice following prenatal cocaine exposure. Furthermore, prenatal cocaine exposure increases frontal cortex reactivity to stress [36] and environmental changes [37] that likely accompany social isolation. From this perspective, one might consider the possibility that PCOC mice may be especially sensitive to the enhancing effect of short-term isolation on social approach, rendering them more likely to engage in longer bouts of social interaction.…”