Retrograde Amnesia Induced by Drugs Acting on Different Molecular Systems.

Rossato, Janine I.; Bonini, Juliana Sartori; Coitinho, Adriana Simon; Vianna, Mônica Ryff Moreira Roca; Medina, Jorge H.; Cammarota, Martı́n; Izquierdo, Iván

doi:10.1037/0735-7044.118.3.563

Cited by 59 publications

(72 citation statements)

References 39 publications

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“…Here, we reported that aripiprazole caused significant changes in STM and LTM in the inhibitory avoidance task, with an improvement in the performance of the animals (longer latency to climb down the platform) when compared to the control group. The inhibitory avoidance task has been used to hypothesize that several biochemical mechanisms may influence memory [22,23] . This task is heavily dependent on the hippocampus, where a sequence of molecular events takes place.…”

Section: Discussionmentioning

confidence: 99%

Neurobehavioral and genotoxic parameters of antipsychotic agent aripiprazole in mice

et al. 2011

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Aim: Aripiprazole is an antipsychotic agent to treat schizophrenia, which acts through dopamine D 2 partial agonism, serotonin 5-HT 1A partial agonism and 5-HT 2A antagonism. This study was designed to evaluate the neurobehavioral effects and genotoxic/mutagenic activities of the agent, as well as its effects on lipoperoxidation. Methods: Open field and inhibitory avoidance tasks were used. Thirty min before performing the behavioral tasks, adult male CF-1 mice were administered aripiprazole (1, 3 or 10 mg/kg, ip) once for the acute treatment, or the same doses for 5 d for the subchronic treatment. Genotoxic effects were assessed using comet assay in the blood and brain tissues. Mutagenic effects were evaluated using bone marrow micronucleus test. Lipoperoxidation was assessed with thiobarbituric acid reactive substances (TBARS). Results: Acute and subchronic treatments significantly decreased the number of crossing and rearing in the open field task. Acute treatment significantly increased the step-down latency for both the short-and long-term memory in the inhibitory avoidance task. Subchronic treatments with aripiprazole (3 and 10 mg/kg) caused significant DNA strain-break damage in peripheral blood but not in the brain. Mutagenic effect was not detected in the acute and subchronic treatments. Nor TBARS levels in the liver were affected. Conclusion: Aripiprazole improved memory, but could impair motor activities in mice. The drug increased DNA damage in blood, but did not show mutagenic effects, suggesting that it might affect long-term genomic stability.Keywords: antipsychotic agent; aripiprazole; locomotion; memory; genotoxic/mutagenic activities; DNA damage; lipoperoxidation Acta Pharmacologica Sinica (2011Sinica ( ) 32: 1225Sinica ( -1232 doi: 10.1038/aps.2011 published online 15 Aug 2011 Original Article * To whom correspondence should be addressed. [8] .In the experimental context, Nagai et al [9] showed that aripiprazole that was administered as either a single dose or as consecutive doses (for 7 d) ameliorated phencyclidine-induced impairment of recognition memory in mice. However, another study showed that aripiprazole impaired the passiveavoidance response at doses near its anti-dopamine ED 50 (7.7 mg/kg, as defined by apomorphine stereotypy). At doses lower than those that affected the passive-avoidance response, aripiprazole was unable to reverse the MK-801-induced impairment in the same task [4] . Therefore, further investigations are necessary to elucidate the effect of aripiprazole on memory.The aim of the present study was to investigate the effects of aripiprazole on memory and on locomotor and exploratory activities with the inhibitory avoidance and open field tasks as behavioral models. Some drugs that affect memory can induce damage in biomolecules, such as lipids and DNA. Therefore, possible cytotoxic and genotoxic effects were evaluated by measuring lipid peroxidation in the liver and DNA strand breaks in both the peripheral blood and brain tissues after behavioral tasks. Mutagenic e...

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Section: Discussionmentioning

confidence: 99%

Neurobehavioral and genotoxic parameters of antipsychotic agent aripiprazole in mice

et al. 2011

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“…It is important to note that SSR180711 reversed the deleterious effects of MK-801 in the object recognition task when the psychotomimetic was administered in the immediate post-acquisition interval, thus affecting consolidation and/or recall processes. It can be speculated that the effects of SSR180711 are mediated via a7 n-AChRs that indirectly mediate glutamate release in the hippocampus and the amygdala, two structures well known to be important for information processing in the post-training period (Rossato et al, 2004). It is important to note that the positive effects of SSR180711 in the object recognition test in mice using a long-term forgetting delay are mediated by the a7 n-AchR, as they were abolished by the genetic deletion of this receptor subtype.…”

Section: Profile Of Ssr180711 In Tests Predictive Of Therapeutic Actimentioning

confidence: 99%

SSR180711, a Novel Selective α7 Nicotinic Receptor Partial Agonist: (II) Efficacy in Experimental Models Predictive of Activity Against Cognitive Symptoms of Schizophrenia

Pichat

Bergis

Terranova

et al. 2006

Neuropsychopharmacol

235

155

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SSR180711 (4-bromophenyl 1,4diazabicyclo(3.2.2) nonane-4-carboxylate, monohydrochloride) is a selective a7 nicotinic receptor (n-AChR) partial agonist. Based on the purported implication of this receptor in cognitive deficits associated with schizophrenia, the present study assessed efficacy of SSR180711 (i.p. and p.o.) in different types of learning and memory involved in this pathology. SSR180711 enhanced episodic memory in the object recognition task in rats and mice (MED: 0.3 mg/kg), an effect mediated by the a7 n-AChR, as it was no longer seen in mice lacking this receptor. Efficacy was retained after repeated treatment (eight administrations over 5 days, 1 mg/kg), indicating lack of tachyphylaxia. SSR180711 also reversed (MED: 0.3 mg/kg) MK-801-induced deficits in retention of episodic memory in rats (object recognition). The drug reversed (MED: 0.3 mg/kg) selective attention impaired by neonatal phencyclidine (PCP) treatment and restored MK-801-or PCP-induced memory deficits in the Morris or linear maze (MED: 1-3 mg/kg). In neurochemical and electrophysiological correlates of antipsychotic drug action, SSR180711 increased extracellular levels of dopamine in the prefrontal cortex (MED: 1 mg/kg) and enhanced (3 mg/kg) spontaneous firing of retrosplenial cortex neurons in rats. Selectivity of SSR180711 was confirmed as these effects were abolished by methyllycaconitine (3 mg/kg, i.p. and 1 mg/kg, i.v., respectively), a selective a7 n-AChR antagonist. Additional antidepressant-like properties of SSR180711 were demonstrated in the forced-swimming test in rats (MED: 1 mg/kg), the maternal separation-induced ultrasonic vocalization paradigm in rat pups (MED: 3 mg/kg) and the chronic mild stress procedure in mice (10 mg/kg o.d. for 3 weeks). Taken together, these findings characterize SSR180711 as a promising new agent for the treatment of cognitive symptoms of schizophrenia. The antidepressant-like properties of SSR180711 are of added interest, considering the high prevalence of depressive symptoms in schizophrenic patients.

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“…The test session step-down latency depends on the intensity of the footshock. Using 0.4-0.5 mA, 2-sec footshock, test step-down latency is usually of about 40 sec; if the training footshock is higher (0.8-1.0 mA the retention score is usually much higher (3 or more min) (Quevedo et al 2005, Cammarota et al 2004, 2005. Inhibition of their natural exploratory tendency to explore beyond the safe area constitutes a conditioned avoidance response; i.e., an instrumental conditioned reflex.…”

Section: Inhibitory Avoidance Learning: Learning Little and Learning mentioning

confidence: 99%

“…Infusion volume was 0.5 μl/side. Infusions lasted 30 sec on each side, and the cannulae were kept in place for an additional 15 sec (Izquierdo et al 1992, Izquierdo and Medina 1997, Cammarota et al 2004, 2005. Some of the treatments were given at the times mentioned before or after a single training session (Tr1) and these animals were tested just once (T1).…”

Section: Inhibitory Avoidance Learning: Learning Little and Learning mentioning

confidence: 99%

“…This task relies heavily on the dorsal hippocampus (Lorenzini et al 1996, Izquierdo andMedina 1997), where it uses a sequence of molecular events very remindful of those of long-term potentiation (Bernabeu et al 1997, Izquierdo and Medina 1995, 1997; but it also depends on the entorhinal and parietal cortex and is intensely modulated by the basolateral nucleus of the amygdala, in all of which it uses other sequences of molecular events (Izquierdo et al 1992, Lorenzini et al 1996, Izquierdo and Medina 1997, Bonini et al 2003, Rossato et al 2004). In the fear conditioning procedures, animals learn to put their skeletal muscles tense and avoid movement (i.e., to freeze) either in response to being placed in a certain compartment (contextual fear) or when an acoustic or other stimulus is given while they are in that compartment ("conditioned fear").…”

Section: Introductionmentioning

confidence: 99%

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A link between the hippocampal and the striatal memory systems of the brain

Rossato

Zinn

Furini

et al. 2006

An. Acad. Bras. Ciênc.

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Two major memory systems have been recognized over the years (Squire 1987): the declarative memory system, which is under the control of the hippocampus and related temporal lobe structures, and the procedural or habit memory system, which is under the control of the striatum and its connections. Most if not all learning tasks studied in animals, however, involve either the performance or the suppression of movement; this, if learned well, may be viewed as having become a habit. It is agreed that memory rules change from their first association to those that take place when the task is mastered. Does this change of rules involve a switch from one memory system to another? Here we will comment on: 1) reversal learning in the Morris water maze (MWM), in which the declarative or spatial component of a task is changed but the procedural component (to swim to safety) persists and needs to be re-linked with a different set of spatial cues; and 2) a series of observations on an inhibitory avoidance task that indicate that the brain systems involved change with further learning.

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Retrograde Amnesia Induced by Drugs Acting on Different Molecular Systems.

Cited by 59 publications

References 39 publications

Neurobehavioral and genotoxic parameters of antipsychotic agent aripiprazole in mice

Neurobehavioral and genotoxic parameters of antipsychotic agent aripiprazole in mice

SSR180711, a Novel Selective α7 Nicotinic Receptor Partial Agonist: (II) Efficacy in Experimental Models Predictive of Activity Against Cognitive Symptoms of Schizophrenia

A link between the hippocampal and the striatal memory systems of the brain

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