Beneficial effects of sigma agonists on the age-related learning impairment in the senescence-accelerated mouse (SAM)

Maurice, Tangui; Roman, François J.; Su, Tsung‐Ping; Privat, Alain

doi:10.1016/0006-8993(96)00565-3

Cited by 69 publications

(43 citation statements)

References 31 publications

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“…The s 1 receptor agonist igmesine (Roman et al, 1990) exerted significant antiamnesic effects in several models of amnesia at the dose of 1 mg/kg i.p. (Maurice et al, 1996). BD1047 is a selective s 1 antagonist (Matsumoto et al, 1995) blocking several s 1 agonist-mediated behaviors at doses of 3 and 10 mg/kg i.p.…”

Section: Experimental Designmentioning

confidence: 99%

σ1 Receptor Ligands and Related Neuroactive Steroids Interfere with the Cocaine-Induced State of Memory

Romieu

Lucas

Maurice

2005

Neuropsychopharmacol

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The present series of experiments examined the involvement of the s 1 receptor and related neuroactive steroids in the memory state induced by a very low dose of cocaine. Using a modified passive avoidance procedure in mice, we examined whether cocaine induces state-dependent (StD) learning. Animals trained and tested with saline or the same dose of cocaine (0.1 or 0.3 mg/kg) showed correct retention, measured using two independent parameters: the retention latency and a ratio between the retention latency and the last training latency. Animals trained with cocaine (0.1 mg/kg) and tested with saline or cocaine (0.03, 0.3 mg/kg), or trained with saline and tested with cocaine, showed altered retention parameters, demonstrating that StD occurred. Therefore, cocaine administered before training produced a chemical state used as an endogenous cue to insure optimal retention. Since s 1 receptor activation is an important event during the acquisition of cocaine reward, we tested several s 1 ligands and related neurosteroids. The s 1 agonist igmesine or antagonist BD1047 failed to produce StD, but modified the cocaine state. Among neuroactive steroids, pregnanolone and allopregnanolone, positive modulators of the g-aminobutyric acid type A (GABA A ) receptor, produced StD. However, steroids also acting as s 1 agonists, dehydroepiandrosterone (3b-hydroxy-5a-androsten-17-one (DHEA)), pregnenolone, or antagonist, progesterone, failed to induce StD but modified the cocaine state. Furthermore, optimal retention was observed with mice trained with (igmesine or DHEA) + cocaine and tested with a higher dose of cocaine, or with mice trained with (BD1047 or progesterone) + cocaine and tested with vehicle. This study demonstrated that: (i) low doses of cocaine induce a chemical state/memory trace sustaining StD; (ii) modulation of the s 1 receptor activation, although insufficient to provoke StD, modulates the cocaine state; (iii) neuroactive steroids exert a unique role in state-dependent vs state-independent learning, via GABA A or s 1 receptor modulation, and are able to affect the cocaine-induced mnesic trace at low brain concentrations.

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Section: Experimental Designmentioning

confidence: 99%

σ1 Receptor Ligands and Related Neuroactive Steroids Interfere with the Cocaine-Induced State of Memory

Romieu

Lucas

Maurice

2005

Neuropsychopharmacol

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“…Emotivity was tested using the standard open-field test (13,14). The apparatus consisted of a circular arena with diameters of 60 cm at the base and 80 cm at the top and a wall with a height of 50 cm.…”

Section: Methodsmentioning

confidence: 99%

Ins2Akita mice exhibit hyperphagia and anxiety behavior via the melanocortin system

Asakawa

Toyoshima²,

Inoue³

2007

Int J Mol Med

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Abstract. Elevated anxiety symptoms have been reported to be present in many patients with diabetes mellitus. The underlying mechanisms by which diabetes mellitus influences behavior remain to be determined. We assessed feeding and anxiety behaviors in spontaneously diabetic Ins2 Akita mice. We measured blood glucose, body weight, and food and water intakes in C57BL/6 heterozygote Ins2Akita mice. The behavioral properties of Ins2 Akita mice were assessed in an open-field test and an elevated plus-maze. The gene expression of hypothalamic neuropeptides was examined in non-fooddeprived Ins2Akita mice. Body weights of the Ins2 Akita mice were less than those of the age-matched C57BL/6 mice, as controls. Food and water intakes were increased in the Ins2 Akita mice. In the open-field test, the Ins2 Akita mice had decreased locomotor activity and increased immobilization time. The Ins2 Akita mice exhibited anxiety behavior in the elevated plus-maze. RT-PCR analysis showed decreased proopiomelanocortin (POMC) mRNA expression and increased agouti-related protein (AGRP) mRNA expression in Ins2Akita mice. There were no significant differences in hypothalamic ghrelin mRNA expression. These observations indicate that Ins2 Akita mice, which are characterized by hypoinsulinemia and hyperglycemia, exhibited hyperphagia and anxiety behavior; the mechanism of action involved the activation of hypothalamic AGRP and the inactivation of hypothalamic POMC. In addition, Ins2Akita mice are a useful model for understanding the mechanisms involved in the psychological complications of diabetes mellitus. Further, melanocortin systems may be therapeutic targets not only for diabetes but also for its associated complications.

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“…These included impairment elicited either by chemically treating the animals respectively with the nicotinic acetycholine receptor blocker mecamylamine [29], the calcium channel blocker nimodipine [30], and the β-amyloid 25-35 aggregate [31], or the model of genetically produced senescenceaccelerated mice [32]. The surprise was that the sigma-1 receptor agonists are active in improving the mnemonic deficit elicited by all the above treatment procedures.…”

Section: Physiological and Pharmacological Actionsmentioning

confidence: 99%

Understanding the Molecular Mechanism of Sigma-1 Receptors: Towards A Hypothesis that Sigma-1 Receptors are Intracellular Amplifiers for Signal Transduction

Su¹,

Hayashi²

2003

Current Medicinal Chemistry

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156

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Although sigma receptors were discovered in 1982, the biochemical and physiological roles of sigma receptors have just begun to unveil. Sigma receptors are non-opioid, non-phencyclidine receptors that contain two subtypes: sigma-1 and sigma-2 receptors. The sigma-1 receptor has been cloned and its sequence does not resemble that of any mammalian protein. Sigma-2 receptors have not been cloned. The focus of this review will be on sigma-1 receptors. Sigma-1 receptors contain 223 amino acids and reside primarily at the endoplasmic reticulum. Sigma-1 receptors exist mainly in the central nervous system, but also in the periphery. Sigma-1 receptor ligands include cocaine, (+)-benzomorphans like (+)-pentazocine and (+)N-allyl-normetazocine (or (+)-SKF-10047), and endogenous neurosteroids like progesterone and pregnenolone sulfate. Many pharmacological and physiological actions have been attributed to sigma-1 receptors. These include the regulation of IP3 receptors and calcium signaling at the endoplasmic reticulum, mobilization of cytoskeletal adaptor proteins, modulation of nerve growth factor-induced neurite sprouting, modulation of neurotransmitter release and neuronal firing, modulation of potassium channels as a regulatory subunit, alteration of psychostimulant-induced gene expression, and blockade of spreading depression. Behaviorally, sigma-1 receptors are involved in learning and memory, psychostimulant-induced sensitization, cocaine-induced conditioned place preference, and pain perception. Notably, in almost all the aforementioned biochemical and behavioral tests, sigma-1 agonists, while having no effects by themselves, caused the amplification of signal transductions incurred upon the stimulation of the glutamatergic, dopaminergic, IP3-related metabotropic, or nerve growth factor-related systems. Thus, it is hypothesized that sigma-1 receptors, at least in part, are intracellular amplifiers creating a supersensitized state for signal transduction in the biological system. HISTORY AND INTRODUCTIONOriginally intending to identify a subtype of opioid receptors, the sigma/opioid receptors as proposed by Martin et al.. [1], Su [2] used the tritiated prototypic sigma/opioid receptor ligand SKF-10047 (N-allyl-normetazocine) in binding assays and identified a protein that has a nanomolar affinity for SKF-10047. Surprisingly though, the protein had no affinity for the opioid antagonist naloxone. This raised a possibility that the protein identified by Su [2] may not be the sigma/opioid receptor proposed by Martin et al..[1] but may represent a new receptor at which SKF-10047 has an affinity. The protein identified by Su [2] was later termed "sigma receptor", with the word "opioid" dropped to differentiate it from the sigma/opioid receptor and the word "sigma" retained for it being identified with the labeled ligand SKF-10047. So far, the sigma/opioid receptor proposed by Martin et al.. has not been clearly identified.The sigma receptor has several peculiarities in its ligand binding profile and its distri...

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Beneficial effects of sigma agonists on the age-related learning impairment in the senescence-accelerated mouse (SAM)

Cited by 69 publications

References 31 publications

σ1 Receptor Ligands and Related Neuroactive Steroids Interfere with the Cocaine-Induced State of Memory

σ1 Receptor Ligands and Related Neuroactive Steroids Interfere with the Cocaine-Induced State of Memory

Ins2Akita mice exhibit hyperphagia and anxiety behavior via the melanocortin system

Understanding the Molecular Mechanism of Sigma-1 Receptors: Towards A Hypothesis that Sigma-1 Receptors are Intracellular Amplifiers for Signal Transduction

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