Effects of F lunarizine and Nitrendipine on Electroconvulsive Shock- and Clonidine-Induced Amnesia

Genkova-Papazova, M.; Petkova, B.; Lazarova-Bakarova, M.; Boyanova, Emanuela; Staneva-Stoytcheva, D

doi:10.1016/s0091-3057(96)00406-6

Cited by 24 publications

(14 citation statements)

References 31 publications

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“…In animals, clonidine has been found to produce memory impairments in several learning paradigms ranging from shuttle box (Hawkins and Monti, 1979;Homayoun et al, 2003) to avoidance tasks (Galeotti et al, 2004;Genkova-Papasova and Lazarova-Bakurova, 1988;Genkova-Papazova et al, 1997) and to cue detection (Smith and Aston-Jones, 2011;Brown et al, 2012). Some studies in humans have also reported memory impairments associated with clonidine administration in healthy subjects (Riekkinen et al, 1999;Hall et al, 2001) and in Alzheimer's disease patients (Jakala et al, 1999a, b).…”

Section: Dosage and Number Of Treatmentsmentioning

confidence: 99%

“…Additionally, a few open-label studies have shown beneficial effects of clonidine in treating some PTSD symptoms (Kinzie and Leung, 1989;Harmon and Riggs, 1996;Ziegenhorn et al, 2009), but none of these studies used clonidine specifically in combination with traumatic memory retrieval. In animal models, the use of clonidine has been found to produce memory impairments in step-down (GenkovaPapasova and Lazarova-Bakurova, 1988;Genkova-Papazova et al, 1997), shuttle box (Hawkins and Monti, 1979;Homayoun et al, 2003), and passive avoidance tasks (Galeotti et al, 2004); however, the use of clonidine to block memory reconsolidation has yet to be investigated.…”

Section: Introductionmentioning

confidence: 99%

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Preclinical Evaluation of Reconsolidation Blockade by Clonidine as a Potential Novel Treatment for Posttraumatic Stress Disorder

Gamache

Pitman

Nader

2012

Neuropsychopharmacol

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Exposure to traumatic events can lead to posttraumatic stress disorder (PTSD). Current PTSD treatments typically only produce partial improvement. Hence, there is a need for preclinical research to identify new candidate drugs and to develop novel therapeutic approaches. Animal studies have indicated that fear memories can be weakened by blocking restabilization after retrieval, a process known as reconsolidation. Furthermore, evidence suggests that there are important alterations of the noradrenergic system in PTSD, and hence it may be of interest to study drugs that target this pathway. Here, we investigated the efficacy of clonidine, an a 2 -adrenoreceptor agonist, to block reconsolidation in an animal model of persistent traumatic memories. Using an auditory fear conditioning paradigm in rats, we tested the efficacy of clonidine to weaken fear memory retention when administered systemically after retrieval. We evaluated dosage, number of treatments, and specificity in reconsolidation blockade. We found that postretrieval administration of clonidine disrupts fear-related memories in a dose-dependent manner and that two treatments are sufficient for maximal memory impairment. Furthermore, we determined that this effect is long lasting and specific to reconsolidation processes as shown by the selectivity to affect reactivated memories and the absence of spontaneous recovery and of postreactivation short-term memory impairment. Our results demonstrate the efficacy of systemic administration of clonidine following retrieval to persistently disrupt fear memory retention through reconsolidation blockade. This study provides important preclinical parameters for future therapeutic strategies involving clonidine to block reconsolidation as a novel treatment for PTSD symptoms.

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Section: Dosage and Number Of Treatmentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Preclinical Evaluation of Reconsolidation Blockade by Clonidine as a Potential Novel Treatment for Posttraumatic Stress Disorder

Gamache

Pitman

Nader

2012

Neuropsychopharmacol

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“…The a 2 -agonists are known to exert a variety of effects on the central nervous system. Central depression usually accompanies therapeutic doses of a 2 -agonists and impairment of cognitive functions is also observed [Voronina et al, 1991;Genzoka-Papazova et al, 1997].…”

Section: Discussionmentioning

confidence: 99%

The novel nootropic compound DM232 (UNIFIRAM) ameliorates memory impairment in mice and rats

Ghelardini

Galeotti

Gualtieri

et al. 2002

Drug Development Research

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The favorable pharmacological profile exhibited by piracetam stimulated the synthesis of related compounds potentially endowed with a higher nootropic potency. The antiamnesic and procognitive activity of DM232 (unifiram), a new compound structurally related to piracetam, was investigated. Mouse passive avoidance and rat Morris water maze and Social learning tests were employed. DM232 (0.001-1 mg kg À1 i.p. -0.01-0.1 1 mg kg À1 p.o.) prevented amnesia induced by scopolamine (1.5 mg kg À1 i.p.), mecamylamine (20 mg kg À1 i.p.), baclofen (2 mg kg À1 i.p.), and clonidine (0.125 mg kg À1 i.p.). Furthermore, The antiamnesic effect of the investigated compound was comparable to that exerted by well-known nootropic drugs such as piracetam (30-100 mg kg À1 i.p.), aniracetam (100 mg kg À1 p.o.), rolipram (30 mg kg À1 p.o.), and nicotine (5 mg kg À1 i.p). DM232 (0.1 mg kg À1 i.p.) was also able to prevent amnesia induced by scopolamine (0.8 mg kg À1 i.p.) in the rat Morris watermaze test. In the rat social learning test, DM232 (0.1 mg kg À1 i.p.) injected in adults rats reduced the duration of active exploration of the familiar partner in the second session of the test. DM232, similarly to piracetam, reduced the duration of hypnosis induced by pentobarbital. At the highest effective doses, the investigated compound did not impair motor coordination (rota rod test), nor modified spontaneous (Animex). These results indicate DM232 (unifiram) as a novel cognition enhancer, strictly related to piracetam-like compounds, able to ameliorate memory impairment at doses about 1,000 times lower than the most active available nootropic compounds. Drug Dev.

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“…α 2 -Agonists also exert a variety of effects on the central nervous system. Central depression usually accompanies therapeutic doses of α 2 -agonists and impairment of cognitive functions is also observed (Voronina et al 1991;Genzoka-Papazova et al 1997).…”

Section: Discussionmentioning

confidence: 99%

DM235 (sunifiram): a novel nootropic with potential as a cognitive enhancer

Ghelardini

Galeotti

Gualtieri

et al. 2002

Naunyn-Schmiedeberg's Archives of Pharmacology

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DM235 (sunifiram), a new compound structurally related to piracetam, prevented the amnesia induced by scopolamine (1.5 mg kg -1 i.p.), after intraperitoneal (0.001-0.1 mg kg -1 ) or oral (0.01-0.1 mg kg -1 ) administration, as shown by a passive avoidance test in mice. The antiamnesic effect of DM235 was comparable to that of well-known nootropic drugs such as piracetam (30-100 mg kg -1 i.p.), aniracetam (100 mg kg -1 p.o.) or rolipram (30 mg kg -1 p.o.). DM235 also prevented mecamylamine (20 mg kg -1 i.p.)-, baclofen (2 mg kg -1 i.p.)-and clonidine (0.125 mg kg -1 i.p.)-induced amnesia in the same test. In the Morris water maze test with rats, scopolamine (0.8 mg kg -1 i.p.) inhibited the reduction of escape latency in both acquisition and retention/retraining tests. DM235 (0.1 mg kg -1 i.p.), 20 min before each daily acquisition training, prevented the scopolamine-induced memory impairment. DM235 (1 mg kg -1 i.p.) also reduced the duration of pentobarbitone-induced hypnosis in mice without modifying the induction time of hypnosis. At the highest effective doses, the investigated compound neither impaired motor coordination (rota-rod test), nor modified spontaneous motility and inspection activity (Animex and hole board tests).These results indicate that DM235, a compound structurally related to piracetam, is a novel nootropic endowed with the capability to prevent cognitive deficits at very low doses. Indeed, its potency is about 1,000 times higher than that of the most active piracetam-like compounds.

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Effects of F lunarizine and Nitrendipine on Electroconvulsive Shock- and Clonidine-Induced Amnesia

Cited by 24 publications

References 31 publications

Preclinical Evaluation of Reconsolidation Blockade by Clonidine as a Potential Novel Treatment for Posttraumatic Stress Disorder

Preclinical Evaluation of Reconsolidation Blockade by Clonidine as a Potential Novel Treatment for Posttraumatic Stress Disorder

The novel nootropic compound DM232 (UNIFIRAM) ameliorates memory impairment in mice and rats

DM235 (sunifiram): a novel nootropic with potential as a cognitive enhancer

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