Effects of diazepam, meprobamate, chlorpromazine and apomorphine on a quickly learned conditioned suppression in mice.

Nagasaka, Mitsuaki; Kameyama, Tsutomu

doi:10.1248/bpb1978.6.523

Cited by 19 publications

(2 citation statements)

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“…The conditioned fear stress has been regarded as an animal model of treatment-resistant psychoses, since anxiolytics and/or antidepressants did not attenuate the mo- tor suppression in conditioned fear stress (Kameyama and Nagasaka 1982;Nagasaka and Kameyama 1983). Taken together, these findings suggest that the decrease in the serum levels of DHEAS is related to the development of conditioned fear stress response and neurosteroids might be useful anti-psychotics for treatment-resistant psychoses.…”

Section: Discussionmentioning

confidence: 99%

“…The anxiolytic actions of this drug have been proposed to be related to an augmentation of GABA A receptor function, although the mechanisms underlying these effects are yet unclear (Bitran et al 1991;Brot et al 1997;Wieland et al 1991). It has been demonstrated that anxiolytics such as diazepam or chlordiazepoxide do not attenuate the motor suppression in conditioned fear stress (Kameyama and Nagasaka 1982;Nagasaka and Kameyama 1983). Thus, it is likely that the conditioned fear stress is resistant to GABA A mimic neurosteroids and agents such as allopregnanolone and benzodiazepines.…”

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Neurosteroids Ameliorate Conditioned Fear Stress An Association with Sigma1 Receptors

Noda

Kamei

et al. 2000

Neuropsychopharmacology

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Mice exhibited a marked suppression of motility (conditioned fear stress) when placed in an environment in which they had previously received an electric footshock. This conditioned fear stress response was dose-dependently attenuated by neurosteroids such as dehydroepiandrosterone sulfate (DHEAS; 25 and 50 mg/kg, s.c.) and pregnenolone sulfate (PREGS; s.c.), and by a putative sigma 1 047; 3 and 6 mg/kg, s.c.). However, progesterone (PROG; s.c.) and allopregnanolone (5 and 20 mg/kg, s.c.) had no effect on this stress response. The attenuating effects of DHEAS (50 mg/kg, s.c.), PREGS (50 mg/kg, s.c.), and ( ϩ )- 047 (6 mg/kg, s.c.) were reversed by i.p.), a sigma 1 receptor antagonist and PROG (5 or 10 mg/kg, i.p.). When DHEAS (25 mg/kg) was co-administered with ( ϩ )- 047 (3 mg/kg) Neurosteroids are synthesized in the brain, either de novo from cholesterol or from steroid hormone precursors, and accumulate in the nervous system to levels that are at least in part independent of steroidogenic gland secretion (Baulieu 1981). Neurosteroids, such as progesterone (PROG), pregnenolone (PREG), dehydroepiandrosterone (DHEA), and their respective sulfate ester (PREGS or DHEAS), are involved in regulating the imbalance between excitation and inhibition in the CNS (Wu et al. 1991). The neurosteroids, allopregnanolone, allotetrahydrodeoxycorticosterone, PREGS, and DHEAS have been shown to possess antistress, anxiolytic, and antiamnesic properties in experimental animal models (Bitran et al. 1991;Brot et al. 1997;Maurice et al. , 1999Urani et al. 1998;Wieland et al. 1991). Recent evidence suggests that DHEAS and PREGS also play an important role in depression. Interestingly, decreased levels of DHEA, DHEAS, and PREGS have been associated with depression, cognitive dysfunction, aging, and other neurological conditions (Orentreich et al. 1984;Vallée et al. 1997), and DHEA improves the depression score in patients (Wolkowitz et al. 1997). However, the From the Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine (YN, HK, YK, TN, TN), Nagoya, Japan; and Department of Clinical Pharmacy, Faculty of Pharmacy, Meijo University (YK, TN, MN), Nagoya, Japan. receptor agonist, ( ϩ )-N-allylnormetazocine (( ϩ )-Address correspondence to: Dr. Toshitaka Nabeshima, Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan.Received October 18, 1999; revised February 2, 2000; accepted February 18, 2000. N EUROPSYCHOPHARMACOLOGY 2000 -VOL . 23 , NO . 3 Neurosteroids and Sigma 1 Receptors 277 mechanism underlying the beneficial effects of neurosteroids is not yet known.Neurosteroids have been shown to affect the activity of neurotransmitter systems, which are involved in a variety of neuropsychiatric illnesses. DHEAS and PREGS are negative allosteric modulators of the ␥ -aminobutyric acid (GABA) A receptors (Majewska 1992), and positive modulators of N-methyl-D-aspartate (NMDA) receptor-mediated res...

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Neurosteroids Ameliorate Conditioned Fear Stress An Association with Sigma1 Receptors

Noda

Kamei

et al. 2000

Neuropsychopharmacology

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A role played by sigma receptors in the conditioned suppression of motility in mice

1988

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Mice exhibited marked suppression of motility (conditioned suppression) when placed in the same environment in which they had previously received an electric footshock. The conditioned suppression was attenuated by cyclazocine and N-allylnormetazocine (SKF-10047), sigma agonists. The effect of these drugs was reduced by chronic pretreatment with cyclazocine. This behavioral change was related to the change in binding activity of [3H]-phencyclidine to sigma receptors (defined using non-radioactive SKF-10047). In the chronic vehicle-pretreated conditioned suppression group, the Kd and Bmax values of [3H]-phencyclidine binding at the high affinity site were increased when compared to those in the chronic vehicle-pretreated control group. The increased values were restored to the control levels by acute treatment with cyclazocine and SKF-10047. On the other hand, in the chronic cyclazocine-pretreated conditioned suppression group, acute cyclazocine and SKF-10047 treatment failed to change the increased values of Kd and Bmax at the high affinity site. The present behavioral and receptor-binding experiments suggest that the activation of nervous system mediated by sigma receptors may be responsible for the attenuation of conditioned suppression of motility.

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Preclinical data on morpholine (3,5-di-tertbutyl-4-hydroxyphenyl) methanone induced anxiolysis

Cabral

Moreira

Rodrigues

et al. 2023

Naunyn-Schmiedeberg's Arch Pharmacol

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Effects of diazepam, meprobamate, chlorpromazine and apomorphine on a quickly learned conditioned suppression in mice.

Cited by 19 publications

References 5 publications

Neurosteroids Ameliorate Conditioned Fear Stress An Association with Sigma1 Receptors

Neurosteroids Ameliorate Conditioned Fear Stress An Association with Sigma1 Receptors

A role played by sigma receptors in the conditioned suppression of motility in mice

Preclinical data on morpholine (3,5-di-tertbutyl-4-hydroxyphenyl) methanone induced anxiolysis

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