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Dopamine 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
Full text linkThe 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
Cumulative effect of norepinephrine and dopamine carrier blockade on extracellular dopamine increase in the nucleus accumbens shell, bed nucleus of stria terminalis and prefrontal cortex
No full textWe investigated, by microdialysis in various brain areas, the possibility that dopamine could be captured by the norepinephrine transporter when the dopamine transporter is pharmacologically blocked. Administration of reboxetine, a selective blocker of the norepinephrine transporter, 20 min after the administration of GBR 12909, a selective blocker of the dopamine transporter, produced an increase of dopamine output in the nucleus accumbes shell (+408% above basal) greater than that obtained by GBR 12909 alone (+308% above basal). On the contrary, reboxetine did not increase further the dopamine output produced by GBR 12909 in the nucleus accumbens core or in the dorsal caudate, areas lacking a consistent noradrenergic innervations. A cumulative effect of dopamine and norepinephrine transporter blockade on the output of dopamine in dialysates was also observed in the bed nucleus of stria terminalis and in the prefrontal cortex. This study shows that dopamine extracellular concentration can be elevated by norepinephrine transporter blockade, even in areas where the dopamine transporter is predominant, when the latter is pharmacologically blocked. This phenomenon may have relevance in psychostimulant dependence as well as in antidepressant pharmacology
Effect of amphetamine, cocaine and depolarization by high potassium on extracellular dopamine in the nucleus accumbens shell of SHR rats. An in vivo microdyalisis study
No full textSpontaneously hypertensive rats (SHR) exhibit behavioural abnormalities (hyperactivity and hyper reactivity to stress) that resemble the behavioural abnormalities of human attention-deficit with hyperactivity disorder (ADHD). Because dopamine has been implicated in ADHD we studied by in vivo microdialysis the dopamine output in the nucleus accumbens (NAc) shell of 6 week-old (pre-hypertensive stage) SHR rats and in their normotensive age matched Wistar Kyoto controls (WKY). We observed that SHR rats had significant higher basal dialysate dopamine concentrations (about 20%) than WKY. Systemic administration of amphetamine (0.25 and 0.5 mg/kg s.c.), and methylphenidate (I and 2 mg/k- i.p.) produced an higher increase in dialysate dopamine in the NAc shell of SHR rats as compared with WKY rats, although only after the administration of the lowest dose of amphetamine and methylphenidate this difference was found to be significant. In contrast when the microdialysis fiber was perfused by 30 or 60 mM K+, a lower increase of dialysate dopamine was observed in SHR rats as compared with WKY rats. These apparently contradictory results can be explained by postulating that SHR rats have a higher tone of NAc shell dopamine transmission and synthesis associated with a lower storage capacity of vesicles in dopamine terminals of the same area. (C) 2003 Elsevier Ltd. All rights reserved
Increase of dialysate dopamine in the bed nucleus of stria terminalis by clozapine and related neuroleptics
No full textNeuroleptics are known to stimulate dopamine release in neostriatal terminal areas. In the present study we have investigated by brain microdialysis in freely mo moving mts the effect of typical and atypical neuroleptics on dopamine transmission in tl-le bed nucleus of stria terminalis, a dopamine terminal area belonging to the limbic system and recently assigned the so-called extended amygdala. Mean basal dialysate dopamine values were 14.3 moles/20 mu l sample. Dopamine output in dialysates was increased dose-by clozapine (max + 158%, 248%, and 461% of basal nt 5, 10, and 20 mg/kg LP, respectively), risperidone (max + 115% and 221% of basal at I and 3 mg/kg IF, respectively, olanzapine (max + 138% and 235% of basal at 3 and 6 mg/kg IF, respectively, BIMG 80 (max) 64% and 164% of basal at 3 and 5 mg/kg IF, respectively, amperozide(max + 110% and 194% of basal at 3 and 6 mg/kg IF, respectively, The selective dopamine D-4 antagonist L-745,870 increased dialysate dopamine but at rather high closes and not as effectively as clozapine (max + + 32%, 89%, and 130% of basal at 2.7, 5.4, and 10.8 mg/kg IF, respectively). The typical neuroleptic haloperidol (0.1 and 0.5 mg/kg SC) and the selective D-2 antagonist raclopride (0.14, 0.56, and 2.1 mg/kg SC), the serotonergic 5-HT2 antagonist ritanserin (0.5 and 1.5 mg/kg IF), and the adrenergic alpha(1) antagonist prazosin (0.91 and 2.73 mg/kg IP) did not affect dialysate dopamine in the bed nucleus of stria terminalis. Saline (I ml/kg SC or 3 ml/kg IF) did not modify dialysate dopamine. Therefore, atypical neuroleptics share the ability of stimulating dopamine transmission in the bed nucleus of stria terminalis, brit this property is not mimicked by any of the! drug tested that selectively act on individual receptors among those that lire affected by atypical neuroleptics These observations raise the possibility that the property of increasing dopamine transmission in the bed nucleus of stria terminalis is the result of combined blockade of dopamine, serotonin, and noradrenaline re receptors and that might be profile predictive of an atypical neuroleptic profile. (C) 1999 American College of Neuropsychopharmacology
A microdyalisis study of dopamine transmission in the nucleus accumbens shell of SHR rats: a model of attention deficit hyperactivity disorder (ADHD)
No full textEffect of Dopamine and Norepinephrine Carrier Blockade on Extracellular Dopamine Release in Rat Brain
No full textStimulation of Dopamine Release in the Bed Nucleus of Stria Terminalis. A Trait of Atypical Antipsychotics?
No full textno abstract availabl
Stimulation of in vivo dopamine transmission in the bed nucleus of stria terminalis by reinforcing drugs
No full textDrugs of abuse preferentially increase dopamine transmission in the shell of the nucleus accumbens. This area is considered as a transition between the striatum and the extended amygdala a complex neural system that includes the central amygdala and the bed nucleus of stria terminalis, areas that, like the nucleus accumbens shell, are heavily innervated by mesolimbic dopamine neurons originating in the ventral tegmental area. Given the anatomical and neurochemical relationships and similarities with the nucleus accumbens shell it was of interest to investigate whether the dopamine transmission of the bed nucleus of stria terminalis shares with the accumbens shell the peculiar responsiveness to drugs of abuse. To this end we studied by microdialysis with concentric probes, the effect of drugs of abuse on extracellular dopamine in the bed nucleus of stria terminalis. We report that morphine, nicotine, cocaine, ethanol, and the selective dopamine uptake inhibitor GBR 12909 increase effectively and dose dependently extracellular dopamine in the bed nucleus of stria terminalis. These results indicate that the bed nucleus of stria terminalis shares with the nucleus accumbens shell a peculiar sensitivity to the dopamine stimulant actions of drugs of abuse
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