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Prenatal cocaine exposure, early experience and later vulnerabilities
367
1998 NBTS ABSTRACTS
findings on response to novel challenges from a cohort of prenatally cocaine-exposed infants and preschool aged children followed longitudinally since birth. Arousal regulation in the face of novel challenges is operationalized behaviorally as state and emotional reactivity and neurophysiologically as the startle response and heart rate variability. Across different ages and tasks, behavioral and neurophysiological findings suggest that prenatally CE children 4 to 5 years of age are more likely to exhibit disrupted arousal regulation. Because the regulation of arousal serves as a gating mechanism to optimize orientation and attention, arousal regulation has important implications for ongoing information processing, learning, and memory. Further, impaired arousal regulation predisposes children to a lower threshold for activation of "stress circuits" and may increase their vulnerability to the developmentally detrimental effects of stressful conditions particularly the chaotic environmental conditions often characterizing substance-abusing families. (Supporled by National Institute on Drug Abuse R01 DA06025 and K02 DA00222 awarded to Dr. Mayes)
NBTS 53 SPEAR, L.P. Department of Psychology and Center for Developmental Psychobiology, Binghamton University, Binghamton, New York. Prenatal cocaine exposure, early experience and later vulnerabilities. Neural compensations occurring after prenatal cocaine exposure may permit some functional recovery, although the cost of this reorganization may be an increase in later vulnerability to cognitive or pharmacological challenges and to environmental demands and stressors. Data using our animal model of gestational cocaine exposure, consisting of s,c. injections of 40 mg/kg cocaine HCl daily from gestational days 8-20, will be reviewed to illustrate these vulnerabilities. Interestingly, offspring exposed prenatally to cocaine may not only be more sensitive to environmental stressors, but may also be unusually susceptible to the long-term effects of early experiences in comparison with control or even undernourished offspring. This potential for early experience to
reverse some consequences of prenatal cocaine exposure, if replicated and extended, may eventually offer promise for early intervention approaches. (Supported by ROI DA04478; K02 DA00140)
NBTS54 DOW-EDWARDS, D. L.; Department of Pharmacology, State University of New York, Brooklyn, NY Ontogenic cocaine effects: Evidence for multifactoral mechanisms Since development begets vulnerability and since the brain develops over a protracted period of pre and postnatal life in the rat and the human, we examined the effects of cocaine exposure during multiple critical periods. Prenatal cocaine generally dampens functional activity and shifts the dopamine D 1:D2 balance. Postnatal cocaine also alters functional activity and the Dl:D2 balance but the directions of the changes depend of the gender of the animal and the time of drug exposure. PND 1120 cocaine dampens D 1 responses within the mesolimbic DA system in males and increases Dl responses within the nigrostriatal system in females. In males 5-HT responsivity is increased while in females it is reduced. In addition, cocaine's effects on brain metabolism appear to depend upon the context in which the study is conducted; a phenomena which resembles impaired function within the locus coeruleus. These and other data support multiple actions of cocaine affecting both DA and 5-HT neuronal populations and hypothetically noradrenergic neurons, as well. These multifactoral effects of cocaine may preclude a simplistic description of a clinical syndrome. Use of sensitive measures and greater effort to control the context in which measurements are collected should improve our ability to identify the biological effects of cocaine in clinical settings.
NBTS 55 HURD*, YL., D. DOW-EDWARDS, 1. BUSH*, and H. MINKOFF*. Dept. Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden and Departments of Pharmacology and Obstetrics & Gynecology, SUNY, Brooklyn, NY The molecular
1998 NBTS ABSTRACTS
findings on response to novel challenges from a cohort of prenatally cocaine-exposed infants and preschool aged children followed longitudinally since birth. Arousal regulation in the face of novel challenges is operationalized behaviorally as state and emotional reactivity and neurophysiologically as the startle response and heart rate variability. Across different ages and tasks, behavioral and neurophysiological findings suggest that prenatally CE children 4 to 5 years of age are more likely to exhibit disrupted arousal regulation. Because the regulation of arousal serves as a gating mechanism to optimize orientation and attention, arousal regulation has important implications for ongoing information processing, learning, and memory. Further, impaired arousal regulation predisposes children to a lower threshold for activation of "stress circuits" and may increase their vulnerability to the developmentally detrimental effects of stressful conditions particularly the chaotic environmental conditions often characterizing substance-abusing families. (Supporled by National Institute on Drug Abuse R01 DA06025 and K02 DA00222 awarded to Dr. Mayes)
NBTS 53 SPEAR, L.P. Department of Psychology and Center for Developmental Psychobiology, Binghamton University, Binghamton, New York. Prenatal cocaine exposure, early experience and later vulnerabilities. Neural compensations occurring after prenatal cocaine exposure may permit some functional recovery, although the cost of this reorganization may be an increase in later vulnerability to cognitive or pharmacological challenges and to environmental demands and stressors. Data using our animal model of gestational cocaine exposure, consisting of s,c. injections of 40 mg/kg cocaine HCl daily from gestational days 8-20, will be reviewed to illustrate these vulnerabilities. Interestingly, offspring exposed prenatally to cocaine may not only be more sensitive to environmental stressors, but may also be unusually susceptible to the long-term effects of early experiences in comparison with control or even undernourished offspring. This potential for early experience to
reverse some consequences of prenatal cocaine exposure, if replicated and extended, may eventually offer promise for early intervention approaches. (Supported by ROI DA04478; K02 DA00140)
NBTS54 DOW-EDWARDS, D. L.; Department of Pharmacology, State University of New York, Brooklyn, NY Ontogenic cocaine effects: Evidence for multifactoral mechanisms Since development begets vulnerability and since the brain develops over a protracted period of pre and postnatal life in the rat and the human, we examined the effects of cocaine exposure during multiple critical periods. Prenatal cocaine generally dampens functional activity and shifts the dopamine D 1:D2 balance. Postnatal cocaine also alters functional activity and the Dl:D2 balance but the directions of the changes depend of the gender of the animal and the time of drug exposure. PND 1120 cocaine dampens D 1 responses within the mesolimbic DA system in males and increases Dl responses within the nigrostriatal system in females. In males 5-HT responsivity is increased while in females it is reduced. In addition, cocaine's effects on brain metabolism appear to depend upon the context in which the study is conducted; a phenomena which resembles impaired function within the locus coeruleus. These and other data support multiple actions of cocaine affecting both DA and 5-HT neuronal populations and hypothetically noradrenergic neurons, as well. These multifactoral effects of cocaine may preclude a simplistic description of a clinical syndrome. Use of sensitive measures and greater effort to control the context in which measurements are collected should improve our ability to identify the biological effects of cocaine in clinical settings.
NBTS 55 HURD*, YL., D. DOW-EDWARDS, 1. BUSH*, and H. MINKOFF*. Dept. Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden and Departments of Pharmacology and Obstetrics & Gynecology, SUNY, Brooklyn, NY The molecular