Transplacental Cocaine Exposure 3

Wilkins, Aaron S.; Marota, John J. A.; Tabit, Eddy; Kosofsky, Barry E.

doi:10.1016/s0892-0362(97)00128-1

Cited by 29 publications

(6 citation statements)

References 33 publications

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“…Cocaine progeny did not differ from saline progeny in their rate of acquisition of the discrimination when the more salient, more intense tone was the CS+, however, they were severely impaired in acquisition of the discrimination when the less intense, less salient tone was the CS+. Regardless of the nature of the discrimination, either cross modal or intramodal, prenatal cocaine exposure significantly retarded the rate of CR acquisition to a less salient CS+ when a more salient stimulus served as the CS- (Romano and Harvey, 1996a;Wilkins et al, 1996).…”

Section: Resultsmentioning

confidence: 95%

“…We conducted two more discrimination experiments, this time involving a discrimination between two tones differing in both frequency and intensity (Wilkins et al, 1996). The intensity dimension was manipulated in order to produce differences in stimulus salience between the two tones since it seemed that differences in stimulus salience rather than modality were contributing to the attentional alterations seen in cocaineexposed animals.…”

Section: Resultsmentioning

confidence: 99%

“…The mouse model of prenatal cocaine exposure shows a similar pattern of apparently normal learning during a simple acquisition task but impaired learning when greater attentional demands are placed on the organism . Adult mice exposed to cocaine prenatally demonstrate normal aversion to an odor paired with a footshock but fail to show blocking of associative learning when a redundant CS is added to the original odor-footshock pair (Wilkins et al, 1996;1998). Blocking of associative learning when a redundant CS is added to an already established CS-US association is often regarded as an attention.al phenomenon whereby animals learn to ignore the redundant CS (Mackintosh, 1975).…”

Section: Discussionmentioning

confidence: 99%

“…9 The enhanced learning is not due to an increase in nonassociative learning such as sensitization or pseudoconditioning 9 Enhanced learning to auditory stimuli is not due to a change in auditory thresholds . 9 Poorer learning is evident as task difficulty is increased (Romano and Harvey, 1996a;Wilkins et al, 1996) 9 Difficulty in preferentially attending to less salient but relevant stimuli when more salient, irrelevant stimuli occur in the same context (Romano and Harvey, 1996;Wilkins et al, 1996). 9 The attentional deficits demonstrated by cocaine progeny may be linked to the developmental abnormalities of the anterior cingulate cortex possibility was investigated by measuring the electrophysiological responses of the anterior cingulate cortex and related brain structures during the acquisition of an instrumental discrimination in the rabbit.…”

Section: Summat'ymentioning

confidence: 99%

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Effects of prenatal exposure to cocaine on the developing brain: Anatomical, chemical, physiological and behavioral consequences

et al. 2001

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Earlier studies of human infants and studies employing animal models had indicated that prenatal exposure to cocaine produced developmental changes in the behavior of the offspring. The present paper reports on the results obtained in a rabbit model of in utero exposure to cocaine using intravenous injections (4 mg/kg, twice daily) that mimic the pharmacokinetics of crack cocaine in humans. At this dose, cocaine had no effect on the body weight gain of dams, time to delivery, litter size and body weight or other physical characteristics of the offspring. In spite of an otherwise normal appearance, cocaine-exposed neonates displayed a permanent impairment in signal transduction via the D1 dopamine receptor in caudate nucleus, frontal cortex and cingulate cortex due to an uncoupling of the receptor from its associated Gs protein. This uncoupling in the caudate nucleus was shown to have behavioral consequences in that young or adult rabbits, exposed to cocaine in utero, failed to demonstrate amphetamine-elicited motor responses normally seen after activation of D1 receptors in the caudate. The cocaine progeny also demonstrated permanent morphological abnormalities in the anterior cingulate cortex due to uncoupling of the D1 receptor and the consequent inability of dopamine to regulate neurite outgrowth during neuronal development. Consistent with the known functions of the anterior cingulate cortex, adult cocaine progeny demonstrated deficits in attentional processes. This was reflected by impairment in discrimination learning during classical conditioning that was due to an inability to ignore salient stimuli even when these were not relevant to the task. The impairment in discrimination learning also occurred in an instrumental avoidance task and could be shown to be due to an impairment of cingulothalamic learning-related neuronal coding. It was proposed that the selective loss of D1-related neurotransmission in the anterior cingulate cortex prevented an appropriate activation of GABA neurons and thus a loss of inhibitory regulation that is necessary for processes involved in associative attention. Taken together, these findings suggest that the uncoupling of the D1 receptor from its G protein may be the fundamental source of the anatomic, cognitive and motor disturbances seen in rabbits exposed to cocaine in utero. Moreover, the long-term cognitive and motor deficits observed in the rabbit model are in agreement with the recent reports indicating that persistent attentional and other behavioral deficits may be evident in cocaine-exposed children as they grow older and are challenged to master more complex cognitive tasks.

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Section: Resultsmentioning

confidence: 95%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Summat'ymentioning

confidence: 99%

See 2 more Smart Citations

Effects of prenatal exposure to cocaine on the developing brain: Anatomical, chemical, physiological and behavioral consequences

et al. 2001

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“…However, the effects of prenatal cocaine exposure on the number and distribution of GABA and projection neurons in the mature cerebral cortex were not known. Therefore, we examined the number and distribution of GABA and projection neurons in the frontal and medial prefrontal cortices of 60-day-old mice that were exposed to cocaine or saline from the 8th day of gestation until the day of birth [14,15]. …”

Section: Introductionmentioning

confidence: 99%

Prenatal Cocaine Exposure Decreases Parvalbumin-Immunoreactive Neurons and GABA-to-Projection Neuron Ratio in the Medial Prefrontal Cortex

McCarthy

Bhide²

2012

Dev Neurosci

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Cocaine abuse during pregnancy produces harmful effects not only on the mother but also on the unborn child. The neurotransmitters dopamine and serotonin are known as the principal targets of the action of cocaine in the fetal and postnatal brain. However, recent evidence suggests that cocaine can impair cerebral cortical GABA neuron development and function. We sought to analyze the effects of prenatal cocaine exposure on the number and distribution of GABA and projection neurons (inhibitory interneurons and excitatory output neurons, respectively) in the mouse cerebral cortex. We found that the prenatal cocaine exposure decreased GABA neuron numbers and GABA-to-projection neuron ratio in the medial prefrontal cortex of 60-day-old mice. The neighboring prefrontal cortex did not show significant changes in either of these measures. However, there was a significant increase in projection neuron numbers in the prefrontal cortex but not in the medial prefrontal cortex. Thus, the effects of cocaine on GABA and projection neurons appear to be cortical region specific. The population of parvalbumin-immunoreactive GABA neurons was decreased in the medial prefrontal cortex following the prenatal cocaine exposure. The cocaine exposure also delayed the developmental decline in the volume of the medial prefrontal cortex. Thus, prenatal cocaine exposure produced persisting and region-specific effects on cortical cytoarchitecture and impaired the physiological balance between excitatory and inhibitory neurotransmission. These structural changes may underlie the electrophysiological and behavioral effects of prenatal cocaine exposure observed in animal models and human subjects.

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