The Maudsley Reactive and Nonreactive strains of rats: A survey

Pl, Broadhurst

doi:10.1007/bf01073201

Cited by 312 publications

(87 citation statements)

References 69 publications

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“…More relevant to the degree of loss of α2-adrenergic receptor function reported here are a series of studies in Maudsley rats. The Maudsley reactive strain have a greater reactivity to stress than rats from the Maudsley non-reactive strain (Broadhurst, 1975), and investigations of the basis for this behavioral difference have revealed that the reactive strain have 30-40% less [ 125 I]para-iodoclonidine binding sites in the LC (Sara et al, 1993), a decreased behavioral response to clonidine (Sara et al, 1993), and an increased noradrenergic response to stress (Buda et al, 1994). Thus, these studies support the contention that the degree of loss of α2-adrenergic binding observed in rats exposed to prenatal cocaine may be linked with the altered Fos and NE turnover measures reported here, and play a role in the altered behavior documented in other studies (Spear et al, 1998, and citations provided in the Introduction).…”

Section: Discussionmentioning

confidence: 99%

Prenatal cocaine exposure enhances responsivity of locus coeruleus norepinephrine neurons: Role of autoreceptors

et al. 2007

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Children exposed to cocaine during gestation have a higher incidence of neurobehavioral deficits. The neurochemical bases of these deficits have not been determined, but the pharmacology of cocaine and the nature of the abnormalities suggest that disruptions in catecholaminergic systems may be involved. In the current study, we used a rat model of prenatal cocaine exposure to examine the impact that this exposure has on the locus coeruleus (LC) noradrenergic system in offspring. Pregnant rats received twice-daily intravenous injections of cocaine (3 mg/kg) or saline between gestational days 10 and 20, and progeny were tested as juveniles. Exposure to a mild stressor elevated an index of norepinephrine turnover in the prefrontal cortex and also increased Fos expression in tyrosine hydroxylase-positive LC neurons in rats exposed to prenatal cocaine but not in rats exposed to prenatal saline. No change in the number of tyrosine hydroxylase-positive neurons in the LC was observed between the two prenatal treatment groups. Specific binding of [ 125 I]-para-iodoclonidine, a radioligand with specificity for high affinity α2A-adrenergic receptors, was decreased in the LC of rats exposed to prenatal cocaine compared to prenatal saline controls. As α 2 -adrenergic receptors on LC norepinephrine neurons function as autoreceptors, their down-regulation by prenatal cocaine exposure provides a plausible mechanism for the observed heightened reactivity of norepinephrine neurons in these animals. These data indicate that prenatal cocaine exposure results in lasting changes to the regulation and responsivity of rat LC norepinephrine neurons. A similar dysregulation of LC norepinephrine neurons may occur in children exposed to cocaine during gestation, and this may explain, at least partly, the increased incidence of cognitive deficits that have been observed in these subjects.

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Section: Discussionmentioning

confidence: 99%

Prenatal cocaine exposure enhances responsivity of locus coeruleus norepinephrine neurons: Role of autoreceptors

et al. 2007

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“…Genetic differences have been reported to influence the occurrence of vocalizations produced in pups (Broadhurst, 1975;Insel & Hill, 1987;Shapiro & Insel, 1990) as observed between pups of the prairie vole, Microtus Ochrogaster and the closely related montane vole Microtus Montanus. In adult rats, individual differences have been observed in treatments that evoke vocalizations in some animals but not others.…”

Section: Defeca T I O Nmentioning

confidence: 99%

Discriminative fear conditioning to context expressed by multiple measures of fear in the rat

Antoniadis

McDonald

1999

Behavioural Brain Research

135

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“…The 10 attributes chosen for this study (Table 2) consist of the variables found most useful for the analysis of open-field behavior throughout many previous studies. The distance from the wall d was shown to measure heritable thigmotactic behavior (Broadhurst, 1975;Leppanen et al, 2005;Lipkind et al, 2004) highly replicable across laboratories . The momentary speed v was shown to be a key variable in the intrinsic categorization of behavior into progression and 'lingering' in both mice ) and rats (Kafkafi et al, 2001).…”

Section: Pattern Array Analysismentioning

confidence: 99%

“…Thus the key to applying a data mining approach in behavioral analysis is designing a useful 'chip', that is, constructing a proper categorization of the data into multiple types of behavior that can be mined. To this end the units employed by PA consist of a large number (B100 000) of complex movement patterns, algorithmically defined as simultaneous combinations of several ethologically relevant 'attributes' such as the distance from the arena wall (Broadhurst, 1975;Leppanen et al, 2005;Lipkind et al, 2004), the speed and acceleration of movement (Kafkafi et al, 2003b), direction of movement (Horev et al, 2007), and turning . For example, by using the three attributes of acceleration, distance from the wall and turning, a specific movement pattern in PA may be defined as the combination 'heavily braking while moving near the wall but turning slightly away from it'.…”

Section: Introductionmentioning

confidence: 99%

A Data Mining Approach to In Vivo Classification of Psychopharmacological Drugs

Kafkafi

Yekutieli

Elmer

2008

Neuropsychopharmacol

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Data mining is a powerful bioinformatics strategy that has been successfully applied in vitro to screen for gene-expression profiles predicting toxicological or carcinogenic response ('class predictors'). In this report we used a data mining algorithm named Pattern Array (PA) in vivo to analyze mouse open-field behavior and characterize the psychopharmacological effects of three drug classesFpsychomotor stimulant, opioid, and psychotomimetic. PA represents rodent movement with B100 000 complex patterns, defined as multiple combinations of several ethologically relevant variables, and mines them for those that maximize any effect of interest, such as the difference between drug classes. We show that PA can discover behavioral predictors of all three drug classes, thus developing a reliable drug-classification scheme in small group sizes. The discovered predictors showed orderly dose dependency despite being explicitly mined only for class differences, with the high doses scoring 4-10 standard deviations from the vehicle group. Furthermore, these predictors correctly classified in a dose-dependent manner four 'unknown' drugs (ie that were not used in the training process), and scored a mixture of a psychomotor stimulant and an opioid as being intermediate between these two classes. The isolated behaviors were highly heritable (h 2 450%) and replicable as determined in 10 inbred strains across three laboratories. PA can in principle be applied for mining behaviors predicting additional properties, such as within-class differences between drugs and within-drug dose-response, all of which can be measured automatically in a single session per animal in an open-field arena, suggesting a high potential as a tool in psychotherapeutic drug discovery.

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The Maudsley Reactive and Nonreactive strains of rats: A survey

Cited by 312 publications

References 69 publications

Prenatal cocaine exposure enhances responsivity of locus coeruleus norepinephrine neurons: Role of autoreceptors

Prenatal cocaine exposure enhances responsivity of locus coeruleus norepinephrine neurons: Role of autoreceptors

Discriminative fear conditioning to context expressed by multiple measures of fear in the rat

A Data Mining Approach to In Vivo Classification of Psychopharmacological Drugs

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