Endogenous homovanillic acid levels differ between rat and rabbit caudate, hippocampus, and cortical regions

Reader, Tomás A.; Dewar, Karen M.

doi:10.1007/bf00965620

Cited by 10 publications

(2 citation statements)

References 28 publications

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“…A rabbit model was chosen for these studies for a variety of reasons: (1) the prior history of the rabbit as a model of behavioral teratology following drug treatment (Denenberg et al, 1982;Hartman, 1974;Hudson and Distel, 1986;Kasirsky and Tansy, 1971); (2) rabbits exhibit patterns of brain development and growth that parallel those of humans (Harel et al, 1972;Hartman, 1974); (3) the rabbit metabolizes dopamine, the neurotransmitter through which cocaine is believed to act, in a similar manner to that in humans and other primates (Reader and Dewar, 1989); (4) the ease of performing multiple intravenous injections of cocaine via the marginal ear vein of the rabbit and thus mimicking the pharmacokinetics of smoking "crack" cocaine, the primary route of administration by pregnant women (Jones, 1990); (5) the sensitivity of the rabbit to the behavioral effects of various drugs is quite similar to that of humans (Denenberg et al, 1982;Harvey, 1987;Schindler and Harvey, 1990); (6) classical conditioning of the rabbit's nictitating membrane (NM) response has become a standard method for examining associative learning and has been demonstrated to exhibit all of the cognitive processes that have been observed in humans (Harvey, 1987;Romano and Harvey, 1992); and (7) the rabbit has been extensively employed to examine the electrophysiological correlates of learning (Gabriel, 1990).…”

Section: The Rabbit Model Of Prenatal Cocaine Exposurementioning

confidence: 93%

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: The Rabbit Model Of Prenatal Cocaine Exposurementioning

confidence: 93%

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

et al. 2001

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“…The rabbit was chosen for these studies for a variety of reasons: (1) the sensitivity of the rabbit to the behavioral effects of various drugs which is similar to that of humans 7,8; (2) the ease of performing multiple drug injections via the marginal ear vein and thus mimicking the pharmacokinetics of smoking “crack” cocaine, the primary route of administration by pregnant women 9; (3) the history of the rabbit as a model of behavioral teratology following drug treatment 7,10–12; (4) the metabolism by the rabbit of dopamine, the neurotransmitter through which cocaine is believed to act, in a similar manner to that in humans and other primates 13; (5) the exhibition by rabbits of patterns of brain development and growth that parallel those of humans 11,14; and (6) classical conditioning of the rabbit's nictitating membrane (NM) response exhibiting all of the cognitive processes that have been observed in humans. 8,15…”

Section: Rabbit Model For Prenatal Exposure To Cocainementioning

confidence: 99%

Prenatal Cocaine Exposure: Long‐Term Deficits in Learning and Motor Performance^a

Romano

Harvey

1998

Annals of the New York Academy of Sciences

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We have developed a rabbit model of in utero exposure to intravenous injections of cocaine given twice daily to dams from gestational days 8-29. At the doses employed (4 mg/kg, injected twice daily), no differences were found in the body weight gain of dams, time to delivery, litter size, and body weight or other physical characteristics of the offspring. However, cocaine-exposed pups displayed an abnormal structural and neurochemical development of the anterior cingulate cortex which persisted into adulthood. In agreement with the known functions of the anterior cingulate cortex, we found that adult, sexually mature rabbits, exposed to cocaine prenatally, demonstrate impairments in motor function, alterations in associative learning and severe impairments in discrimination learning. Moreover, the alterations in discrimination learning were interpreted to be due to deficits in attentional processes. Specifically, cocaine progeny preferentially attend to more salient stimuli even when these are not relevant to the task. Consequently they have difficulty in attending to less salient but relevant stimuli when more salient but irrelevant stimuli occur in the same context. We concluded that the learning deficits are a reflection of the morphologic and neurochemical abnormalities of the anterior cingulate cortex. Alterations in dopamine function of the caudate nucleus may also contribute to the deficits in motor performance.

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Dopamine D1 and D2 receptors in the forebrain ofDystonia musculorum mutant mice: An autoradiographic survey in relation to dopamine contents

Ongali

Ase

Hébert

et al. 2000

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Dystonia musculorum (dt(J)/dt(J)) mutant mice suffer from a degeneration of spinocerebellar tracts as well as a dystrophy of peripheral sensory tracts. This neurological mutant has been proposed as an animal model of human cerebellar ataxia, in particular of the Friedreich's type; thus, it was deemed of interest to examine the endogenous contents of dopamine (DA) and metabolites as well as the distribution of DA receptors of the D(1) and D(2) subtypes, in order to delimit the biochemical characteristics of this pathological disorder, and determine an eventual dopaminergic dysfunction in this mutant. Tissue DA and its major metabolites 3, 4-dihydroxyphenylacetic acid, homovanillic acid and 3-methoxytyramine were measured by HPLC coupled to electrochemical detection in six cortical regions, in four divisions of rostral neostriatum and two halves of caudal neostriatum, as well as in olfactory bulb, nucleus accumbens, septum, amygdala, hippocampus, thalamus, hypothalamus, brainstem, cerebellum, substantia nigra, and ventral tegmental area. The only significant difference between dt(J)/dt(J) mice and wild-type controls was an increase in hypothalamic DA contents (+47%). Quantitative autoradiography with [(3)H]SCH23390 and [(3)H]raclopride, to label D(1) and D(2) receptors, respectively, revealed only moderate changes in receptor densities in a few localized regions. In dt(J)/dt(J) mutants, D(1) receptor numbers were found to be higher in thalamus (+27%) as well as in the medio-dorsal (+16%) and in the latero-dorsal (+16%) quadrants of rostral neostriatum, while D(2) receptor densities were greater in the medio-ventral (+32%) and the latero-dorsal (+17%) quadrants. The present results indicate an overall conservation of dopaminergic functions, albeit the few localized sites of increased D(1) and D(2) receptor densities, and that are seemingly independent of the DA innervation pattern, as revealed by the tissue measurements of DA and metabolites. They also rule out a major pathology linked to deficits in DA neurotransmission, and validate this mutant as an animal model of human cerebellar ataxia, probably of the Friedreich type.

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Endogenous homovanillic acid levels differ between rat and rabbit caudate, hippocampus, and cortical regions

Cited by 10 publications

References 28 publications

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

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

Prenatal Cocaine Exposure: Long‐Term Deficits in Learning and Motor Performance^a

Dopamine D1 and D2 receptors in the forebrain ofDystonia musculorum mutant mice: An autoradiographic survey in relation to dopamine contents

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Endogenous homovanillic acid levels differ between rat and rabbit caudate, hippocampus, and cortical regions

Cited by 10 publications

References 28 publications

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

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

Prenatal Cocaine Exposure: Long‐Term Deficits in Learning and Motor Performancea

Dopamine D1 and D2 receptors in the forebrain ofDystonia musculorum mutant mice: An autoradiographic survey in relation to dopamine contents

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Product

Resources

About

Prenatal Cocaine Exposure: Long‐Term Deficits in Learning and Motor Performance^a