Effects of repeated administration of chlordiazepoxide on spontaneous locomotor activity in mice

Sansone, Mario

doi:10.1007/bf00431999

Cited by 48 publications

(11 citation statements)

References 13 publications

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“…However, pups locomotor activity was increased by CDP administration, an effect more pronounced at the lower doses. Increases in locomotion by BDZ agents have been explained as reflecting "anxiolytic" effects of these drugs, while the general "taming" effect on behavior caused by these drugs is believed to be associated with their sedative actions (Sansone, 1979;Gardner & Piper, 1982). We did not observe a biphasic effect of different doses of CDP on locomotion as was found for UVZ.…”

Section: Discussionmentioning

confidence: 43%

“…We did not observe a biphasic effect of different doses of CDP on locomotion as was found for UVZ. This is most likely due to the lack of higher CDP doses than the 15 mg/kg dose (Sansone, 1979). The increase in the time spent lying still following CDP administration does not seem to be compatible with the parallel increase in locomotion caused by this drug.…”

Section: Discussionmentioning

confidence: 92%

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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: 43%

Section: Discussionmentioning

confidence: 92%

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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“…An apparatus consisting of eight opaque Plexiglas toggle-floor boxes, divided into two compartments with an opening at the floor level, has also been used to measure the exploratory ambulation (crossings of the opening); in this experimental situation chlordiazepoxide (5 mg' kg -I i. p.) produced stimulation of activity in naive mice, the effect being strongly pronounced at the commencement of the testing session and declining thereafter (VETULANI and SANSONE, 1978). Using the same apparatus, SANSONE (1979) found that repeated administration of chlordiazepoxide to mice enhanced the stimulant action oflower doses but reduced the depressant effect of higher doses. He concluded that tolerance developed to the depressant but not to the stimulant effects of chlordiazepoxide.…”

Section: Decrease In Ratsmentioning

confidence: 93%

General Pharmacology and Neuropharmacology of Benzodiazepine Derivatives

Haefely¹,

Pieri²,

Polc³

et al. 1981

Handbook of Experimental Pharmacology

114

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“…A significant increase of locomotor activity is induced by DZP in rats that have been treated repeatedly and for protracted periods of time with large doses of DZP (35). These rats exhibit a decrease of ␣1 and an increase of ␣5 GABA A -R subunit expression in the cortex and hippocampus but no changes in GABA A -R number (31).…”

Section: The Paradoxical Action Of Dzp and Imd Is Likely Mediated By ␣5mentioning

confidence: 99%

“…These rats exhibit a decrease of ␣1 and an increase of ␣5 GABA A -R subunit expression in the cortex and hippocampus but no changes in GABA A -R number (31). Thus, one could infer that the paradoxical locomotor hyperactivity elicited by IMD or DZP in SI mice is due to a reduction of neophobia, probably elicited by stimulation of the overexpressed ␣5-containing GABA A -Rs (15,(35)(36)(37)(38) in the absence of sedative action due to the decrease of GABA A -R-containing ␣1 subunits.…”

Section: The Paradoxical Action Of Dzp and Imd Is Likely Mediated By ␣5mentioning

confidence: 99%

Imidazenil and diazepam increase locomotor activity in mice exposed to protracted social isolation

Pinna

Agís‐Balboa

Zhubi

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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In cortex and hippocampus, protracted (>4 weeks) social isolation of adult male mice alters the subunit expression of GABA type A receptors (GABA A-Rs) as follows: (i) the mRNAs encoding GABAA-R ␣1, ␣2, and ␥2 subunits are decreased by Ϸ50%, whereas those encoding ␣4 and ␣5 subunits are increased by Ϸ100%; (ii) similarly, the synaptic membrane expression of the ␣1 subunit protein is down-regulated, and that of the ␣5 subunit protein is up-regulated; and (iii) the binding of [ 3 H]flumazenil to hippocampal synaptic membranes is decreased. Behaviorally, socially isolated (SI) mice are resistant to the sedative effects of the positive allosteric GABA A-R modulators diazepam (DZP) and zolpidem. This resistance seems to be attributable to the decrease of ␣1-containing GABAARs. Paradoxically, DZP, which, unlike zolpidem, acts at ␣5-containing GABA A-Rs, increases the locomotor activity of SI mice. Imidazenil, which fails to modulate ␣1-, ␣4-, and ␣6-containing GABAA-Rs but is a selective positive allosteric modulator of ␣5-containing GABAA-Rs, also increases locomotor activity in SI mice. Importantly, SI mice responded to muscimol, 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3(2H)-one, and allopregnanolone similar to group-housed mice. These data suggest that a switch (a decrease in ␣1͞␣2 and ␥2 and an increase in ␣4 and ␣5 subunits) in the composition of the heteropentameric GABAA-R subunit assembly without a change in total GABAA-R number occurs during social isolation. Thus, the repertoire of DZP and imidazenil actions in SI mice appears to be elicited by the allosteric modulation of GABAA-Rs overexpressing ␣5 subunits. Benzodiazepine response mediated by ␣1-containing GABAA-Rs is expected to be silent or reduced. GABAA receptors ͉ nested RT-PCR

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Effects of repeated administration of chlordiazepoxide on spontaneous locomotor activity in mice

Cited by 48 publications

References 13 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

General Pharmacology and Neuropharmacology of Benzodiazepine Derivatives

Imidazenil and diazepam increase locomotor activity in mice exposed to protracted social isolation

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