1,721,077 research outputs found
MICRODIALYSIS COUPLED WITH ELECTROCHEMICAL DETECTION: A WAY TO INVESTIGATE BRAIN MONOAMINE ROLE IN FREELY MOVING ANIMALS
No full textDopamine reuptake by norepinephrine neurons: exception or rule?
No full textCrit Rev Neurobiol. 2004;16(1-2):121-8.
Dopamine reuptake by norepinephrine neurons: exception or rule?
Carboni E, Silvagni A.
Department of Toxicology and Centre of Excellence on Neurobiology of Addiction,
University of Cagliari, Cagliari, Italy. [email protected]
Dopamine reuptake by norepinephrine terminals can occur in brain areas such as
the prefrontal cortex, the nucleus accumbens shell, and the bed nucleus of stria
terminalis that are innervated, although unevenly, by both dopamine and
norepinephrine neurons. Therefore the antidepressants that bind selectively the
norepinephrine transporter might produce their therapeutic effect by raising the
extracellular concentration of dopamine besides that of norepinephrine. Moreover,
cocaine can be reinforcing even in knock-out mice for the dopamine transporter
because it might raise synaptic dopamine in the nucleus accumbens shell by
preventing its uptake by the norepinephrine transporter, an effect that could
take place even in wild animals. Recently, it has also been suggested that
dopamine can be co-released with norepinephrine by norepinephrine neurons,
although it is not clear whether this feature might be related to a previous
nonspecific uptake of dopamine by the norepinephrine transporter. In this review
we discuss the potential role of the nonspecific uptake of dopamine by
norepinephrine transporter in the mechanism of action of drugs of abuse,
antipsychotics, and antidepressants.
PMID: 15581407 [PubMed - indexed for MEDLINE
Experimental investigations on dopamine transmission can provide clues on the mechanism of the therapeutic effect of amphetamine and methylphenidate in ADHD.
No full textNeural Plast. 2004;11(1-2):77-95.
Experimental investigations on dopamine transmission can provide clues on the
mechanism of the therapeutic effect of amphetamine and methylphenidate in ADHD.
Carboni E, Silvagni A.
Department of Toxicology, Centro di Eccellenza sulla Neurobiologia delle
Dipendenze University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy.
[email protected]
The aim of this review is to compare the experimental evidence obtained from in
vitro studies on the effect of amphetamine and methylphenidate on dopamine
transmission with the results obtained in animal models of attention deficit
hyperactivity disorder (ADHD). This comparison can extend the knowledge on the
mechanism of action of the drugs used in the therapy of ADHD and provide insight
into the etiology of ADHD. In particular, we considered the results obtained from
in vitro methods, such as synaptosomes, cells in culture, and slices and from in
vivo animal models of ADHD, such as spontaneous hypertensive rats (SHR) and the
Naples high-excitability (NHE) rat lines. The different experimental approaches
produce consonant results and suggest that in SHR rats, in contrast to Wistar
Kyoto rats (WKY), amphetamine and depolarization by high K+ might release
different pools of dopamine-containing vesicles. The pool depleted by amphetamine
might represent dopamine that is stored in large dense core vesicles, whereas
dopamine released by high K+ might be contained in small synaptic vesicles (SSV).
The sustained dopamine transmission observed in the nucleus accumbens of SHR but
not WKY rats can be supported by an elevated synthesis and release, which also
might explain the stronger effect of methylphenidate on dopamine release in SHR
but not in WKY rats. This hypothesis might enlighten the common therapeutic
effect of these drugs, although their action takes place at different levels in
catecholaminergic transmission.
PMCID: PMC2565436
PMID: 15303307 [PubMed - indexed for MEDLINE
CONDITIONED PLACE PREFERENCE: A SIMPLE METHOD FOR INVESTIGATING REINFORCING PROPERTIES IN LABORATORY ANIMALS
No full textDifferent classes of antidepressants share the ability to increase dopamine and norepinephrine release in the bed nucleus of stria terminalis: A possible role in antidepressant therapy?
No full textSerotonin release estimated by transcortical dialysis in freely-moving rats.
No full textThe transcerebral dialysis method has been utilized for measuring extracellular brain concentrations of serotonin and 5-hydroxyindolacetic acid. Dialysis fibres were implanted transversally in the rat frontal cortex and perfused by Ringer. Serotonin and 5-hydroxyindolacetic acid were quantified by reverse phase high performance liquid chromatography with electrochemical detection. Experiments were performed in freely-moving rats 20-24 h after the implant of the fibre. Basal output of serotonin and 5-hydroxyindolacetic acid was 0.12 and 22.8 pmol in 20 min, respectively. The output of serotonin was calcium-dependent and tetrodotoxin-sensitive (1 micron in the Ringer) while was stimulated by veratridine (50 microns) and by high concentrations of K+ (60 and 100 mM). Serotonin output was increased in a concentration-dependent manner by chlorimipramine (1-10 microM) in the Ringer; this drug stimulated serotonin release also when administered s.c. (20 mg/kg) in a tetrodotoxin-sensitive manner. The irreversible monoamine-oxidase inhibitor pargyline (75 mg/kg, i.p.) strongly stimulated serotonin output while reduced 5-hydroxyindolacetic acid output. A proposed serotonin releaser, fenfluramine (25 mg/kg, s.c.), stimulated serotonin release and this effect was strongly potentiated by local application of tetrodotoxin (1 microM). Agonists of serotonin receptors such as lisuride (0.03 mg/kg, s.c.), 8-hydroxy-2-(di-n-propilamino)tetraline (0.25 mg/kg, s.c.) and 5-methoxy 3(1,2,3,6-tetrahydro-4-pyridinil)-1H indole succinate (1 mg/kg, s.c.) reduced serotonin release. It appears that brain dialysis is a suitable method for the study of serotonin release in the cortex of freely-moving rats
BDNF Alterations in Brain Areas and the Neurocircuitry Involved in the Antidepressant Effects of Ketamine in Animal Models, Suggest the Existence of a Primary Circuit of Depression
Full text linkMajor depressive disorder is one of the primary causes of disability and disease worldwide. The therapy of depression is prevalently based on monoamine reuptake blockers; consequently, investigations aimed to clarify the aetiology of depression have mostly looked at brain areas innervated by monamines and brain circuitry involved in inputs and outputs of these areas. The recent approval of esketamine as a rapid-acting antidepressant drug in treatment-resistant depression, has definitively projected glutamatergic transmission as a key constituent in the use of new drugs in antidepressant therapy. In this review we have examined the role of several brain areas: namely, the hippocampus, the medial Prefrontal Cortex (mPFC), the nucleus accumbens (NAc), the Lateral Habenula (LHb), the amygdala and the Bed Nucleus of Stria Terminalis (BNST). The reason for undertaking an in-depth review is due to their significant role in animal models of depression, which highlight their inter-connections as well as their inputs and outputs. In particular, we examined the modification of the expression and release of the brain derived neurotrophic factor (BDNF) and associated changes in dendritic density induced by chronic stress in the above areas of animal models of depression (AnMD). We also examined the effectiveness of ketamine and standard antidepressants in reversing these alterations, with the aim of identifying a brain circuit where pathological alteration might trigger the appearance of depression symptoms. Based on the role that these brain areas play in the generation of the symptoms of depression, we assumed that the mPFC, the NAc/Ventral Tegmental Area (VTA) and the hippocampus form a primary circuit of depression, where regular performance can endure resilience to stress. We have also examined how this circuit is affected by environmental challenges and how the activation of one or more areas, including amygdala, LHb or BNST can produce local detrimental effects that spread over specific circuits and generate depression symptoms. Furthermore, we also examined how, through their outputs, these three areas can negatively influence the NAc/VTA-PFC circuit directly or through the BNST, to generate anhedonia, one of the most devastating symptoms of depression
Dihydropyridine binding sites regulate calcium influx through specific voltage-sensitive calcium channels in cerebellar granule cells.
No full textIn primary cultures of cerebellar granule cells, [3H]nitrendipine binds with high affinity to a single site (KD 1 nM and Bmax 20 fmol/mg protein). The 1,4-dihydropyridine (DHP) class of compounds such as nitrendipine, nifedipine, and BAY K 8644 displace [3H]nitrendipine binding at nanomolar concentrations. Verapamil partially inhibits whereas diltiazem slightly increases the [3H]nitrendipine binding. In these cells, the calcium influx that is induced by depolarization is very rapid and is blocked by micromolar concentrations of inorganic calcium blockers such as cadmium, cobalt, and manganese. The calcium influx resulting from cell depolarization is potentiated by BAY K 8644 and partially inhibited (approximately 40%) by nitrendipine and nifedipine. Other non-DHP voltage-sensitive calcium channel (VSCC) antagonists, such as verapamil and diltiazem, completely blocked the depolarization-induced calcium influx. This suggested that nitrendipine and nifedipine block only a certain population of VSCCs. In contrast, verapamil and diltiazem do not appear to be selective and block all of VSCCs. Perhaps some VSCCs can be allosterically modulated by the binding site for the DHPs, whereas verapamil and diltiazem may block completely the function of all VSCCs by occupying a site that differs from the DHP binding site
The interrelationship between dopamine and noradrenaline in the prefrontal cortex: From physiology to therapy
No full textDopamine release and noradrenaline release in the prefrontal cortex are required for the control of neurobiological functions, whose alteration is considered to be critical in the aetiology of widespread diseases such as schizophrenia, depression and attention deficit hyperactivity disorder (ADHD). The therapeutic agents used in treating these diseases may either increase or reduce dopamine and noradrenaline transmission by acting at receptor or at reuptake site level. The capacity of noradrenaline terminals to capture dopamine by means of the noradrenaline transporter (NET) has opened up new perspectives on the mechanism of action of norepinephine reuptake blockers such as long-established antidepressants or the new therapeutic agent for ADHD, atomoxetine. On the other hand, the hypothesis that dopamine and noradrenaline may be co-released from noradrenaline terminals in the prefrontal cortex suggests an additional interpretation of experimental evidence on the regulation of both dopamine and noradrenaline release through the pre-synaptic 2 receptor. Moreover, the high affinity of noradrenaline for the dopamine D4 receptor and its role in the prefrontal cortex, as well as the capacity of atypical antipsychotics to increase both noradrenaline and dopamine release in this area of the brain, support the hypothesis that dopamine-noradrenaline interaction may have a crucial role in the aetiology and in the therapy of schizophrenia. This chapter will illustrate and discuss the evidence for and against the hypothesis that there is an interdependence between dopamine and noradrenaline transmission in the prefrontal cortex, taking into consideration some recent evidence from our laboratory on the effect of chronic treatment with methylphenidate and atomoxetine on dopamine and noradrenaline release in the prefrontal cortex
Estimation of in-vivo neurotransmitter release by brain microdialysis: the issue of validity
No full textAlthough microdialysis is commonly understood as a method of sampling low molecular weight compounds in the extracellular compartment of tissues, this definition appears insufficient to specifically describe brain microdialysis of neurotransmitters. In fact, transmitter overflow from the brain into dialysates is critically dependent upon the composition of the perfusing Ringer. Therefore, the dialysing Ringer not only recovers the transmitter from the extracellular brain fluid but is a main determinant of its in-vivo release. Two types of brain microdialysis are distinguished: quantitative micro-dialysis and conventional microdialysis. Quantitative microdialysis provides an estimate of neurotransmitter concentrations in the extracellular fluid in contact with the probe. However, this information might poorly reflect the kinetics of neurotransmitter release in vivo. Conventional microdialysis involves perfusion at a constant rate with a transmitter-free Ringer, resulting in the formation of a steep neurotransmitter concentration gradient extending from the Ringer into the extracellular fluid. This artificial gradient might be critical for the ability of conventional microdialysis to detect and resolve phasic changes in neurotransmitter release taking place in the implanted area. On the basis of these characteristics, conventional microdialysis of neurotransmitters can be conceptualized as a model of the in-vivo release of neurotransmitters in the brain. As such, the criteria of face-validity, construct-validity and predictive-validity should be applied to select the most appropriate experimental conditions for estimating neurotransmitter release in specific brain areas in relation to behaviou
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