Evidence for the absence of impulse-regulating somatodendritic and synthesis-modulating nerve terminal autoreceptors on subpopulations of mesocortical dopamine neurons (original) (raw)
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Brain Research, 1974
Thierry et al. 16 described dopamine (DA) stores in the cortex cerebri and were the first to suggest the existence of cortical DA nerve terminals. Subsequent pharmaco-histochemical studies using recent sensitive modifications of the Falck-Hillarp technique2,6,13 together with DA-fi-hydroxylase inhibitors 15 and L-DOPA combined with peripheral decarboxylase inhibitors after reserpine pretreatment have confirmed and extended this study to show that cortical DA nerve terminals probably exist but mainly in the limbic cortex and in the deep layers of the frontal cortex 7,s,11,12. In order to obtain information as to the origin of these cortical DA nerve terminals, lesions have been made in the ventromedial tegmental area of the midbrain, rich in DA nerve cell bodies (group A9-A10 according to DahlstrSm and Fuxe 4) and in the hypothalamic catecholamine (CA) cell group A13 a,5 localized in the dorsal hypothalamus. Male Sprague-Dawley rats (body wt. 150-250 g) have been used. Most of the electrolytic lesions (0.5 mA DC, 30 sec, unipolar) were performed in the area between the A9 and A10 group (Fig. 1). The coordinates were according to K6nig and KlippeP as follows: A (anterior) = +2.0 mm; L (lateral) = + 1.0 mm; V (vertical) ~-2.8 mm. Unilateral intracerebral injections with 6-hydroxydopamine (6-OH-DA, 16 #g/8 /~1) were also performed (A-+ 2.5; L = + 1.2; V =-2.4). Two rats received electrolytic lesions in the midline (L = 0) at the same level and depth as above in order to destroy mainly the A10 group. Also a lateral lesion with the same electrical parameters as above was made in one rat in order to avoid lesioning the A10 group (A = +1.95; L = +1.8; V =-2.8). The A13 group was lesioned in two rats using the following coordinates: A = +4.9 mm; L = +0.6 m m ; V =-1.8 mm. In this case the DC current was 1 mA. All the lesions were unilateral and the non-lesioned side served as a control. The degree of anterograde degeneration of the DA systems to the forebrain was studied 2-3 weeks following the lesion. The DA nerve terminals were distinguished from the noradrenaline (NA) and 5-hydroxytryptamine (5-HT) nerve terminals by using the recent discovery that in the forebrain reserpine-resistant accumulations of CA seem to occur exclusively in the DA nerve terminals 7,11. Some rats were therefore pretreated with reserpine (5-10 mg/kg, i.p.) 18-24 h before killing.
Heterogeneity of the mesotelencephalic dopamine fibers: physiology and pharmacology
Neuroscience & Biobehavioral Reviews, 2000
The mesotelencephalic dopamine (DA) system is heterogeneous with respect to nuclei, terminal loci, DA receptor subtypes, electrophysiological characteristics and response patterns, and neuropharmacological response to a range of agents. The majority of mesocortical and mesolimbic DA neurons originate in the ventral tegmental area. Mesostriatal DA neurons originate in substantia nigra pars compacta. DA neurons originating from the retrorubal field primarily innervate subcortical limbic and neostriatal loci. Mesostriatal terminal loci have relatively low densities of D3 and D4 receptors, compared to mesolimbic and mesocortical loci. The D1 and D2 receptors appear more homogeneously distributed. Electrophysiologically, mesostriatal DA neurons show more regularity in firing pattern (fewer bursting events), and a lower basal firing rate than mesolimbic or mesocortical neurons. Neuropharmacologically, mesocortical DA neurons are less responsive to intravenous d-amphetamine, (ϩ)apomorphine, and chronic antipsychotic drug treatment. Mesocortical DA neurons are also relatively insensitive to iontophoretically applied DA, a finding congruent with their reported relative lack of somatodendritic autoreceptors. Neurochemically, mesoaccumbens DA neurons are more sensitive to systemic administration of drugs with addictive liability. ᭧
Firing modes of midbrain dopamine cells in the freely moving rat
Neuroscience, 2002
AbstractöThere is a large body of data on the ¢ring properties of dopamine cells in anaesthetised rats or rat brain slices. However, the extent to which these data relate to more natural conditions is uncertain, as there is little quantitative information available on the ¢ring properties of these cells in freely moving rats. We examined this by recording from the midbrain dopamine cell ¢elds using chronically implanted microwire electrodes. (1) In most cases, slowly ¢ring cells with broad action potentials were profoundly inhibited by the dopamine agonist apomorphine, consistent with previously accepted criteria. However, a small group of cells was found that were di⁄cult to classify because of ambiguous combinations of properties.
Differential expression of autoreceptors in the ascending dopamine systems of the human brain
Proceedings of the National Academy of Sciences of the United States of America, 1994
The tone and regulation of the brain dopaminergic projections are, in part, determined by the presence or absence of dopamine (DA) autoreceptors: rate of DA synthesis and turnover, as well as both pattern and rate of neuronal firing, are modulated by the expression and activity of these autoreceptors. The expression of dopaminergic receptors in the midbrain DA cell groups, presumably reflecting DA autoreceptors, was determined in the brains of the rat, Old World monkey, and human. In the rat, both the substantia nigra (A9) and the ventral tegmental area (A10) appear to express DA autoreceptors. In the monkey and human, however, only the projections arising from the substantia nigra express these receptors; the limbic projections originating in the ventral tegmental area lack this substrate for DA autoregulation. These results indicate that in the human, the nigrostriatal and mesocorticolimbic dopamine systems may be differentially autoregulated.
The Biphasic Effect of L -DOPA on the Electric Activity of an Isolated Dopaminergic Neuron
Doklady Biological Sciences, 2005
The metabolic precursor of dopamine L -3,4-dihydroxyphenylalanine ( L -DOPA), is widely used in clinics, as well as in experiments with vertebrates and invertebrates, to enhance the activity of the dopaminergic system. In many models, including animals without the blood-brain barrier, L -DOPA causes stronger and more stable effects than dopamine . Recently, it was shown that there were cells that synthesize and release L -DOPA into the extracellular medium in the vicinity of dopaminergic neurons in the hypothalamus of mammals . However, the mechanisms of the effect of extracellular L -DOPA on the dopaminergic system have not been studied well. The purpose of this work was to study the effect of extracellular L -DOPA on the electric activity of dopaminergic cell.
Brain Research, 1987
Effects of dopamine on the rat caudate nucleus neurons were examined in a slice preparation using an intracellular recording technique. Perfusion of the bath with a low concentration (1 gM) of dopamine produced a depolarization concomitant with an increase in the spontaneous firing and the number of action potentials evoked by a depolarizing pulse applied into the cells. In contrast, higher concentrations (100-500/~M) of dopamine inhibited the spontaneous and current-induced firings without apparent effects on the resting membrane potential. In addition, during application of a high concentration (100 t~M) of dopamine there was a marked elevation of the threshold potential of the action potential elicited by a higher depolarizing current. Simultaneous application of lialoperidol (0.5-5/~M) antagonized both excitatory and inhibitory effects induced by the low and high concentrations of dopamine, respegtively. In addition, the excitatory effect induced by a low concentration (1/~M) of dopamine was antagonized by domperidone (0.5/,M), a selective D 2 receptor antagonist, while the inhibitory effect by a high concentration (100 #M) was blocked by SCH 23390, a selective D 1 receptor antagonist. These results strongly suggest that the postsynaptic sites of candate nucleus neurons have at least two subtypes of dopamme receptors (D 1 and D 2 receptors) that mediate inhibitory and excitatory responses of the neuron to dopamine, respectively. Recent receptor-binding analysis revealed that dopamine receptors in the striatum can be classified into at least two subtypes, the D~ receptor, which links with adenylate cyclase, and the D 2 receptor, which does not link with. or even inhibits, the enzyme activity 7A8. Based on these biochemical findings, we recently carried out electrophysiological studies using selective D~ or D2 receptor agonists and antagonists to resolve the discrepancy that the effects of dopamine iontophoretically applied were the opposite of those of SN stimulation 27°28. Our results suggested that D t and D 2 receptors coexisted in the same CN neurons, and mediated the inhibitory and excitatory responses of the neurons, respectively. Biochemical studies have demonstrated that the Correspondence: A. Akaike.
Neuroscience, 1983
Electrophysioiogical recordings from the cells of the neostriatum in rats anaesthetised with halothane revealed only inhibitory actions of dopamine applied iontophoretically close to the cells. Inhibition of cortical driving seemed to have a slightly higher threshold in most cells but dopamine inhibited spontaneous action potentials, glutamate-induced responses, and cortical driving in the cells studied. Fluphenazine applied iontophoretically blocked the actions of dopamine but was itself without effect on the neuronal responses. Sulpiride, in contrast, was without effect on the spontaneous activity of the cells and was ineffective in blocking the action of applied dopamine. Sulpiride, nevertheless, increased the response to cortical stimulation though it had no action on the response to applied glutamate. These results suggest that the sub-class of dopamine receptors on the terminals of the corticostriatal pathway may be inhibitory on glutamate release and preferentially sensitive to blockade by sulpiride. While several different binding sites for dopamine have been described in the central nervous system6," the number of receptors at which dopamine can be shown to exert a physiological effect is considerably smaller in mammals.'3.27,40 In their simpler scheme, Kebabian and Calne17 suggested that sites at which there is a known biochemical effect of dopamine on adenylate cyclase be called D, receptors while the binding sites for dopamine-at that time not associated with known biochemical changes in the post synaptic elements-be called D, receptors. With this simplified scheme it is possible to suggest from lesion studies that the two "receptors" in the neostriatum may in fact be preferentially located on different neuronal elements. The D, receptors are associated with neurones of the neostriatum and with those which project to the substantia nigra (SN). They appear to be associated with the outer membrane of these neurones and are present on their terminals in the SN as well as on their cell bodies in the striatum.32 Kainic acid lesions which destroy the neurones of the striatum, also reduce the activity of adenylate cyclase in the nucleus and result in a 94% reduction in the stimulation of the enzyme by dopamine? Such lesions of the striatum lead to a reduction of the dopamine ligand binding sites in the striatum, presumably as a result of the destruction of striatal neurones.20- .