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Biomedical subjects

S Akhondzadeh

Publications and source records attributed to S Akhondzadeh.

31 records · Page 2Linked to original sources
PubMed1999

Prevention of muscimol-induced long-term depression by brain-derived neurotrophic factor.

1. The authors have recently reported a new protocol for inducing long-term depression through activation of GABAA receptors in the hippocampal slices. This long-term depression is reversed by bicuculline and potentiated by neurosteroids such as alphaxalone. It was also shown that glutamate receptor activity is not involved in the induction of this novel type of long-term depression. Brain derived neurotrophic factor is a member of the neurotrophins family widely expressed in the central nervous system. There is increasing evidence that indicate an important role for brain-derived neurotrophic factor in synaptic plasticity. It has been reported that brain-derived neurotrophic factor level is downregulated by GABA system. The present study investigated a possible relation between muscimol-induced long-term depression and brain-derived neurotrophic factor level. 2. Extracellular recordings were made in the CA1 pyramidal cell layer of rat hippocampal slices following orthodromic stimulation of Schaffer collateral fibers in stratum radiatum. 3. It was observed that brain-derived neurotrophic factor at concentration that did not have any effect itself on the population spike, prevents the induction of long-term depression by muscimol. In addition to this, K-252a an inhibitor of Trk type kinase blocked the prevention of muscimol-induced LTD by brain-derived neurotrophic factor. 4. The results suggest that there is an interaction between muscimol-induced long-term depression and brain-derived neurotrophic factor and may explain the post receptor mechanism of muscimol-induced long-term depression through a bilateral relation between GABAA activity and brain-derived neurotrophic factor.

Animals↗
PubMed1999

Cyproheptadine in treatment of chronic schizophrenia: a double-blind, placebo-controlled study.

OBJECTIVE: There is growing interest in investigating the role of 5-HT receptors in the physiopathology of schizophrenia in particular the negative symptoms. Indeed, newer atypical antipsychotics which interact with 5-HT receptors are more effective in the treatment of negative symptoms compared to typical neuroleptics. We undertook a trial to investigate whether the combination of haloperidol with cyproheptadine, a relatively safe serotonin-blocking agent was more effective than haloperidol alone. METHODS: Thirty patients who met the DSM IV criteria for chronic schizophrenia completed the study. Patients were allocated in a random fashion, 15 each to haloperidol 30 mg/day plus cyproheptadine 24 mg/ day and haloperidol 30 mg/day plus placebo. RESULTS: Although both protocols significantly decreased the positive and negative symptom score over the trial period, the combination of haloperidol and cyproheptadine showed significant superiority over haloperidol alone in the treatment of the negative symptoms. CONCLUSION: Cyproheptadine is a relatively safe compound and may be of therapeutic benefit in treating negative symptoms of schizophrenia in combination with typical neuroleptics. However, a larger study to confirm our results is warranted.

Adult↗
PubMed1999

Hippocampal synaptic plasticity and cognition.

Discoveries made over the past 20 years have greatly improved our understanding of how the brain functions. This article focuses on the relation between memory and cellular mechanisms of neuronal and synaptic plasticity in the hippocampus. Several studies indicate that the hippocampal formation is a crucial element of the neurobiological bases of higher cognitive function. Severe damage to the hippocampal formation is known to produce seemingly permanent anterograde amnesia. A generally accepted hypothesis in neurobiology has been that long-lasting activity-dependent changes in the efficacy of synaptic transmission in the mammalian brain are considered to be of fundamental importance for the development of neural circuitry and for the storage of information. The most compelling and reliable model for such changes has been long-term potentiation (LTP) and long-term depression (LTD) in the hippocampus. Therefore, the possibility of the discovery and development of compounds that, by modulating hippocampal synaptic plasticity, would be useful for the management of dementia and amnesia.

Amnesia↗
PubMed1999

Piracetam in the treatment of schizophrenia: implications for the glutamate hypothesis of schizophrenia.

OBJECTIVE: There is a growing interest in investigating the role of glutamate receptors in the pathophysiology of schizophrenia. Indeed, the hyperdopaminergic theory of schizophrenia can explain only the positive symptoms of schizophrenia, whereas the glutamate hypothesis may provide a more comprehensive view of the illness. We undertook a trial to investigate whether the combination of haloperidol with piracetam, a nootropic agent which modulates the glutamate receptor positively was more effective than haloperidol alone. METHODS: Thirty patients who met the DSM IV criteria for schizophrenia completed the study. Patients were allocated in a random fashion, 14 to haloperidol 30 mg/day plus piracetam 3200 mg/day and 16 to haloperidol 30 mg/day plus placebo. RESULTS: Although both protocols significantly decreased the score of the positive symptoms, the negative symptoms, the general psychopathological symptoms and the total score of PANSS scale over the trial period, the combination of haloperidol and piracetam showed a significant superiority over haloperidol alone in the treatment of schizophrenic patients. CONCLUSION: Piracetam, a member of the nootropic class of drugs and a positive modulator of glutamate receptor, may be of therapeutic benefit in treating schizophrenic patients in combination with typical neuroleptics. However, a larger study to confirm our results is warranted

Adolescent↗
PubMed1998

Potentiation of muscimol-induced long-term depression by benzodiazepines and prevention or reversal by pregnenolone sulfate.

We have recently reported a new protocol for inducing long-term depression through activation of GABAA receptors in the hippocampal slices. This long-term depression is reversed by bicuculline and potentiated by neurosteroids such as alphaxalone. It was also shown that glutamate receptor activity or extracellular calcium are not involved in the induction of this type of long-term depression. The present study investigated the possible relation between muscimol-induced long-term depression and barbiturates/benzodiazepine-induced amnesia and attempts to determine the possible effect of pregnenolone sulfate on muscimol-induced long-term depression. Extracellular recordings were made in the CA1 pyramidal cell layer of rat hippocampal slices following orthodromic stimulation of Schaffer collateral fibres in stratum radiatum (0.01 Hz). It was observed that pentobarbital, benzodiazepines and pregnanolone at concentrations that did not have any effect themselves on the population spike, potentiate the ability of muscimol to induce long-term depression. In addition to this, the long-term depression was either blocked or reversed by pregnenolone sulfate at concentrations (10 microM) where pregnenolone sulfate did not induce any multiple burst or increase of spike size. The results suggest that the potentiation of this type of long-term depression by benzodiazepines and barbiturates can explain the main adverse effect of these drugs, amnesia and cognitive impairment. Moreover, the prevention or reversal of this type of long-term depression by pregnenolone sulfate, may suggest a clinical application of this agent in the management of amnesia or dementia.

Amnesia↗
PubMed1998

Combination of clomipramine and nortriptyline in the treatment of obsessive-compulsive disorder: a double-blind, placebo-controlled trial.

OBJECTIVE: There is growing interest in investigating noradrenergic functions in obsessive-compulsive disorder (OCD) because some antidepressants with strong effects on serotonin reuptake blockade fail to relieve obsessive-compulsive symptoms. We undertook a trial to investigate whether the combination of clomipramine with nortriptyline was more effective than clomipramine alone. METHOD: Thirty patients who met the DSM-IV criteria for OCD completed the study. Patients were allocated in a random fashion, 15 each to clomipramine 150 mg/ day plus nortriptyline 50 mg/day and clomipramine 150 mg/day plus placebo. RESULTS: Although both protocols significantly decreased the scores of the Yale-Brown obsessive-compulsive scale over the trial period, the combination of clomipramine and nortriptyline showed a significant superiority over clomipramine alone in the treatment of OCD. CONCLUSION: As this study indicates, a rapid onset of action is one of the advantages of this combination. This study supports further investigation of the noradrenergic-serotonergic hypothesis in OCD.

Adrenergic Uptake Inhibitors↗
PubMed1996

Glutamate-independent long term depression in rat hippocampus by activation GABAA receptors.

Long-term depression (LTD) of synaptic transmission is a candidate for a neuronal model of forgetting and is considered to be important in learning and memory. The present study employed extracellular recording in the CA1 pyramidal cell layer of rat hippocampal slices following orthodromic stimulation of Schaffer collateral fibres in stratum radiatum. Muscimol induced a time and concentration-dependent LTD at a frequency of stimulation of 0.01 Hz or in the absence of stimulation. The LTD was reversed by stimulation at 1 Hz. The ability of muscimol to act via GABAA receptors was confirmed by the ability of bicuculline (5 microM) to reverse the LTD. The NMDA non-selective glutamate antagonists kynurenate, failed to modify the LTD. receptor antagonist 2-AP5, the selective metabotropic antagonist L(+)AP3 and the non-selective glutamate antagonists kynurenate, failed to modify the LTD. (1S,3R)-ACPD, a selective agonist at metabotropic receptors, did not induce LTD. The lack of involvement of glutamate receptors in muscimol induced LTD in our protocol may indicate a novel type of long-lasting synaptic depression

2-Amino-5-phosphonovalerate↗
PubMed1996

Maintenance of muscimol-induced long-term depression by neurosteroids.

1. The present study was undertaken to expand investigations of the interaction between neurosteroids and long-term depression (LTD) induced by muscimol 10 mu M. 2. Extracellular recordings were made in the CA1 pyramidal cell layer of rat hippocampal slices following orthodromic stimulation of Schaffer collateral fibres in stratum radiatum (0.01 Hz) 3. As previously reported, muscimol at 10 mu M induced a time, frequency of stimulation and concentration-dependent LTD of the amplitude of orthodromic potentials. Alphaxalone, at concentrations that had no significant effect themselves on the population spike (0.5 and 1 mu M) potentiated the inhibitory effect of muscimol on the population spike size. 4. It is now reported that low concentrations of alphaxalone are able to potentiate the ability of muscimol to induce LTD. In addition, concentrations of muscimol as low as 1 mu M which are not themselves able to induce LTD, as well as aiphaxalone and 5 alpha-pregnan-3 alpha-ol-20-one 1 mu M were able to maintain the LTD induced by muscimol 10 mu M 5. It is suggested that the ability of such low concentrations of GABA receptor agonists to maintain LTD could be of physiological importance.

Anesthetics↗
PubMed1996

Muscimol-induced long-term depression in the hippocampus: lack of dependence on extracellular calcium.

We have recently reported a new protocol for inducing long-term depression through activation of GABAA receptors in the hippocampal site. This long-term depression is reversed by bicuculline and potentiated by neurosteroids such as alphaxalone and 5 alpha-pregnan-3 alpha-ol-20-one. It was also shown that glutamate receptor activity is not involved in the induction of this type of long-term depression. The present study investigates the role of calcium in the induction of this novel form of long-term depression and attempts to determine the mechanism of reversal of muscimol-induced long-term depression. Extracellular recordings were made in the CA1 pyramidal cell layer of rat hippocampal slices following orthodromic stimulation of Schaffer collateral fibres in stratum radiatum (0.01 Hz). It was observed that the muscimol-induced long-term depression can be obtained in the absence of calcium in the bathing medium. In addition to this, the long-term depression was reversed by N-methyl-D-aspartate, kainic acid, high potassium medium, veratrine and the calcium ionophore A23187 but not high calcium (10 mM) medium. High potassium medium in the absence of calcium reversed the long-term depression induced by muscimol 10 microM. The results suggest that this type of glutamate-independent long-term depression can be induced in the absence of extracellular calcium. Extracellular calcium is not necessary for reversal of the long-term depression, although when intracellular calcium levels are raised, as by A23187, this is capable of inducing reversal.

Animals↗
PubMed1995

Potentiation by neurosteroids of muscimol/adenosine interactions in rat hippocampus.

Extracellular recordings were made from the CA1 pyramidal cell layer of hippocampal slices in response to stimulation of Schaffer collateral fibres in stratum radiatum. Alphaxalone and 5 alpha-pregnan-3 alpha-ol-20-one potentiated the inhibitory effect of muscimol on the population spike size at low concentrations (0.5 and 1 microM) that had no significant effect on the spike size by themselves. This profile is in agreement with other reports which have described the effect of these neurosteroids as barbiturate-like. Alphaxalone and 5 alpha-pregnan-3 alpha-ol-20-one also at low concentrations potentiated the inhibitory effect of adenosine alone and in the presence of 1 mM barium which blocked adenosine activated potassium channels. Alphaxalone failed to potentiate the inhibitory effect of adenosine in the presence of 1 microM bicuculline. It is concluded that these neurosteroids enhanced the potentiative interaction between adenosine and muscimol in the presence of barium. The results indicate that adenosine's effects are normally enhanced by virtue of the potentiative interaction occurring with endogenous GABA.

Adenosine↗
PubMed1995

Induction of a novel form of hippocampal long-term depression by muscimol: involvement of GABAA but not glutamate receptors.

1. Unlike long-term potentiation, long-term depression (LTD) in the central nervous system remains poorly understood. The present study was undertaken to investigate the role of GABAA receptors in LTD and synaptic plasticity. 2. Extracellular recordings were made in the CA1 pyramidal cell layer of rat hippocampal slices following orthodromic stimulation of Schaffer collateral fibres in stratum radiatum (0.01 Hz). 3. Muscimol induced a time- and concentration-dependent LTD of the amplitude of orthodromic potentials. Increasing the stimulation frequency from 0.01 Hz to 1 Hz for 10 s reversed the LTD induced by muscimol. Muscimol also induced LTD in the absence of electrical stimulation. 4. Adenosine decreased the spike size in a concentration-dependent manner, but failed to induce LTD. 5. Alphaxalone and 5 alpha-pregnan-3 alpha-ol-20-one at concentrations that did not have any effect themselves on the population spike (0.5 and 1 microM), potentiated the inhibitory effect of muscimol on the population spike size, including concentrations which were not effective by themselves. Both steroids were able to potentiate the ability of muscimol to induce LTD. 6. Bicuculline, 5 microM, reversed the LTD induced by muscimol, 10 microM. 7. The NMDA receptor antagonist (+/-)-2-amino-5-phosphonopentanoic acid (2-AP5), the NMDA/metabotropic antagonist 2-AP3 and selective metabotropic antagonist L-(+)-2-amino-3-phosphonopropionic acid (L(+)-AP3) failed to modify the LTD. Similarly, quisqualic acid and (1S, 3R)-aminocyclopentane dicarboxylic acid (ACPD) a selective agonist at metabotropic receptors did not induce LTD or short-term depression, whereas kynurenic acid prevented the reversal of the LTD obtained at 1 Hz. 8. It is concluded that LTD can be induced by the selective activation of GABAA receptors. The lack of involvement of glutamate receptors in our protocol confirms the unique nature of the LTD described here. The phenomenon of GABA-induced LTD and its reversal by 1 Hz stimulation may represent a novel type of long-lasting depression by which inhibitory interneurones can modulate pyramidal cell excitability in a frequency-dependent manner.

Action Potentials↗
PubMed1994

Interaction between adenosine and GABAA receptors on hippocampal neurones.

Extracellular recordings were made from the CA1 pyramidal cell layer of hippocampal slices in response to stimulation of Schaffer collateral fibres in stratum radiatum. Adenosine and muscimol induced concentration-dependent reductions in the amplitude of orthodromically induced population potentials. In order to eliminate effects of these agents on potassium channels, experiments were performed in the presence of barium, 1 mM. This concentration increased potential size, and reduced the inhibitory effect of adenosine on population spike size, but not synaptic potential size. This profile is consistent with the blockade of potassium channels associated only with the postsynaptic effects of adenosine. Muscimol responses were unaffected. Adenosine potentiated the ability of muscimol to inhibit evoked potentials in the absence or presence of barium. The potentiation was prevented by the A1 selective antagonist 8-cyclopentyltheophylline. The effects of adenosine as well as muscimol were reduced by the chloride channel blockers DIDS, which also prevented the adenosine potentiation of muscimol. The results indicate the ability of adenosine to operate chloride channels in hippocampal neurones, and suggest a potentiative interaction between adenosine and muscimol which may also involve chloride channels.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗