Effects of chlordiazepoxide, flumazenil and DMCM on plasma catecholamine and corticosterone concentrations in rats

Boer, Sietse F. de; Gugten, Jan Ban Der; Slangen, Jef L.

doi:10.1016/0091-3057(91)90583-n

Cited by 18 publications

(6 citation statements)

References 34 publications

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“…CDP has been reported to affect CORT secretion in the adult rat. Moderate to high doses of CDP increase CORT levels in rats under basal conditions, but can prevent CORT elevations resulting from exposure to a novel environment (De Boer et al, 1990, De Boer, Van der Gugten, & Slangen, 1991. Because deprived animals show a much greater activation of the HPA axis in response to novelty than nondeprived infants, we expected CDP administration to increase CORT levels in nondeprived animals, while preventing or diminishing CORT secretion in response to novelty and to the injection procedure in maternally deprived infants.…”

Section: Discussionmentioning

confidence: 99%

Behavioral and hormonal responses to stress in the newborn mouse: Effects of maternal deprivation and chlordiazepoxide

Cirulli

Santucci

Laviola

et al. 1994

Developmental Psychobiology

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These studies investigated behavioral and hormonal responses to stress in developing mice. Experiment 1 examined the effects of 24-hr maternal deprivation on corticosterone (CORT) secretion and ultrasonic vocalization (UVZ) rate in 4-, 8-, and 12-day-old mice. At these ages, exposure to a novel environment resulted in minimal changes in CORT secretion. Maternal deprivation increased pups' CORT secretion in an age-dependent fashion but did not affect their UVZ rate. The aim of experiment 2 was to test the effects of chlordiazepoxide (CDP), an anxiolytic compound, on CORT secretion and UVZ in both normally reared and in maternally deprived 8-day-old mice. CDP administration elevated CORT secretion in a dose-dependent fashion, producing larger CORT increases in deprived (DEP) animals. CDP affected UVZ only in nondeprived (NDEP) animals: UVZ rate was decreased by high CDP doses. Overall, these findings demonstrate that the infant mouse shows a period of stress hyporesponsiveness similar to the rat and that maternal presence contributes to inhibit adrenocortical activity. CDP administration, but not novelty exposure, increased CORT secretion in 8-day-old normally reared mice suggesting that during the stress hyporesponsive period, the HPA axis is capable of responding only to specific stimuli. Changes in HPA axis activity and UVZ rate resulting from maternal deprivation and/or CDP challenge do not seem to be directly related.

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Section: Discussionmentioning

confidence: 99%

Behavioral and hormonal responses to stress in the newborn mouse: Effects of maternal deprivation and chlordiazepoxide

Cirulli

Santucci

Laviola

et al. 1994

Developmental Psychobiology

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“…During stress conditions, brain benzodiazepine receptors appear to participate in the physiological regulation of adrenocortical and neurosympathetic activities (De Boer et al, 1990). Moreover, many authors demonstrated that benzodiazepine receptor ligands with an anxiolytic action, such as diazepam, can prevent stressinduced activation of HPA and sympatho-adrenomedullary system (De Boer et al, 1991;Feenstra et al, 1995;Pericic and Pivac, 1996;Wilson et al, 2004). However, our data showed that long-term diazepam treatment of individually housed rats acted by decreasing elevated basal plasma ACTH levels, whereas elevated basal plasma COR remained unchanged in comparison with the corresponding controls.…”

Section: Biochemical Parametersmentioning

confidence: 99%

Behavioral and endocrine responses of socially isolated rats to long-term diazepam treatment

Dronjak¹,

Spasojević²,

Gavrilović³

et al. 2007

Acta vet. (Beogr.)

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The effects of diazepam (0.2 mg/kg/ during 21 days, i.p.) on behavior, pituitary-adrenocortical and sympatho-adrenomedullary system of socially isolated and group-housed adult male rats additionally exposed to immobilization, were studied. Social isolation led to a shorter duration of grooming and longer latency to start grooming. Diazepam in social isolated rats reduced incorrect transitions percentage, but the number of grooming bouts, duration and latency to start grooming remained unchanged. Long-term isolation significantly elevated plasma ACTH and corticosterone, while not affecting noradrenaline and adrenaline. Diazepam decreased only plasma ACTH. Social isolation and immobilization significantly elevated all examined hormones. Immobilization of diazepam-treated isolated rats enhanced plasma ACTH , the increase being significantly lower, comparing to isolated vehicle-treated rats. Immobilization significantly increased plasma adrenaline, noradrenaline and corticosterone of diazepam- or vehicle-treated socially isolated rats. No differences in adrenaline, noradrenaline and corticosterone level between these two groups were observed. This indicates that chronic diazepam treatment of socially isolated rats changes some grooming behavior parameters, but insignificantly affects stress-related adrenomedullary and adrenocortical alterations

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“…The resulting toxicity observed may result in stress responses that involve the release of corticosterone. In addition, there is evidence that drugs that produce novel sensations or alterations in perception in rodents can cause a stress response (De Boer et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Characterization of the Action of Drug-Induced Stress Responses on the Immune System: Evaluation of Biomarkers for Drug-Induced Stress in Rats

Pruett

Hébert

Lapointe

et al. 2007

Journal of Immunotoxicology

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Toxicological testing of compounds often is conducted at the maximum tolerated dose to identify potential target organs. Toxicities observed at these high doses may result in decreased body weight gain, food consumption and activity. These clinical signs are often associated with a generalized stress response. It has been known that stress may cause increased levels of corticosterone, which causes changes in circulating leukocyte profiles, decreases in thymus and spleen weights and changes in the microscopic structure of lymphoid organs. This makes it difficult to differentiate between stress-related changes and direct toxicity to the immune system in standard non-clinical toxicity testing in rats. In mice, MHC Class II expression was found to be a very sensitive biomarker of stress and maybe useful for the rat. Therefore, the objective of studies presented was to further characterize the effects of corticosterone and stressors on the immune system and identify potential biomarkers of stress in rats. Rats were treated with exogenous corticosterone (20 or 30 mg/kg BID) or ethanol (5 g/kg) for either 1 or 4 days. Restraint stress was also evaluated for a 3-day period. Blood and urine samples were collected during the treatment period for corticosterone measurements. At necropsy, blood samples for leukocyte differentials were collected. Spleen and thymus weights, cellularity, lymphocyte subpopulations and histopathology were also evaluated. Urine corticosterone levels were also investigated as a surrogate to measuring serum corticosterone. The results demonstrate that the pattern of responses to corticosterone or the stressors is different in mice and rats. Although, decreases in MHC Class II were found to be a sensitive indicator of stress in mice, only slight decreases were observed in rats with similar serum corticosterone AUC levels. Decreases in thymus weight were greater than spleen weight with corticosterone or ethanol or restraint stressor. No other single parameter or combination of parameters tested were obvious candidates as sensitive biomarkers of stress in rats. However, the good correlation between urine and serum corticosterone levels suggest that urine corticosterone may be a potential biomarker of stress induced changes to the immune response.

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Effects of chlordiazepoxide, flumazenil and DMCM on plasma catecholamine and corticosterone concentrations in rats

Cited by 18 publications

References 34 publications

Behavioral and hormonal responses to stress in the newborn mouse: Effects of maternal deprivation and chlordiazepoxide

Behavioral and hormonal responses to stress in the newborn mouse: Effects of maternal deprivation and chlordiazepoxide

Behavioral and endocrine responses of socially isolated rats to long-term diazepam treatment

Characterization of the Action of Drug-Induced Stress Responses on the Immune System: Evaluation of Biomarkers for Drug-Induced Stress in Rats

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