Biomedical subjects

T A Reader

Publications and source records attributed to T A Reader.

At least 91 records · Page 5Linked to original sources

PubMed1989

Intrathecal bradykinin acts presynaptically on spinal noradrenergic terminals to produce antinociception in the rat.

In the awake restrained rat the intrathecal (i.th.) administration of 8.1 pmol-8.1 nmol of bradykinin (BK) and kallidin (KD) enhanced the reaction time (RT) to a noxious radiant heat stimulus in a dose-dependent manner. The fragments BK-(1-8) and BK-(1-7) were active only at doses higher than 10 nmol and the following rank order of potency was observed: BK greater than KD much greater than BK-(1-8) greater than BK-(1-7). The increment of tail-flick latency was greatest at 1 (BK) or 6 (KD) min and the RT returned to basal levels within 15 min post-administration. The effect of BK (81 pmol) was unaffected by the prior i.th. administration of propranolol and naloxone but was significantly potentiated by prazosin (P less than 0.05). In contrast, the response to BK was significantly blocked (P less than 0.001) by phentolamine, idazoxan and yohimbine as well as by treatment with 6-hydroxydopamine (6-OHDA) at a dose of 20 micrograms (i.th.) 1 week earlier. The latter pretreatment reduced the antinociceptive effect of i.th. tyramine (7 mumol) and potentiated that to noradrenaline (NA) (0.6 nmol) (P less than 0.01) while it preserved both the antinociceptive effect of neurokinin B (8 nmol) and the hyperalgesic effect of substance P (6.5 nmol). A biochemical analysis revealed that 6-OHDA treatment reduced the NA content in the lumbar spinal cord by 60% without affecting the levels of serotonin, dopamine, adrenaline or their main metabolites. There were also significant reductions in NA content in cervical (44%) and thoracic (55%) spinal cord. Pretreatment with 6-OHDA for a longer survival period (2 weeks) caused a further decrease of NA in the lumbar spinal cord (88%); however, the serotonin and dopamine levels were reduced in all regions examined. These results suggest that BK (kinins) may inhibit spinal nociceptive sensory transmission and produce analgesia by acting presynaptically on terminals of bulbospinal NA-containing fibers.

Adrenergic alpha-Antagonists↗

PubMed1989

Acute effects of lithium on catecholamines, serotonin, and their major metabolites in discrete brain regions.

The acute effects of lithium on the central catecholamine and serotonin systems were investigated in well-defined cortical areas in the rat: the anterior cingulate cortex (CIN), the piriform-entorhinal region (PiEn), and the primary visual area (VIS) as well as in the hippocampus (HIP), the neostriatum (CPU; caudateputamen), and the olfactory bulbs (OBs). In these microdissected regions, the catecholamines noradrenaline (NA) and dopamine (DA), the indoleamine 5-hydroxytryptamine (5-HT; serotonin), as well as some of their major metabolites (3-methoxy-4-hydroxyphenylglycol; 3,4-dihydroxyphenylacetic acid; homovanillic acid; 3-methoxytyramine; 5-hydroxy-1-tryptophan; and 5-hydroxyindole-3-acetic acid) were assayed by using high-performance liquid chromatography (HPLC) with electrochemical detection. One hour after the administration of lithium chloride (2 and 10 mEq/kg; i.p.) the endogenous NA levels increased in the CIN and PiEn cortices, in the HIP, and in the CPU. The DA contents remained unchanged in the CPU, HIP, OB, and VIS cortex but were increased in the CIN and PiEn regions. These increases in cortical DA levels were accompanied by reductions in HVA and DOPAC. The levels of HVA and DOPAC but not 3-MT were also reduced in the CPU, in spite of a normal DA content. The discrepancies between changes of DA and the levels of its metabolites indicate changes in the turnover rates as well as an action of lithium on DA synthesis and/or storage in the nigrostriatal and mesocortical systems. The 5-HT contents were also increased by lithium throughout all regions, except for the OB.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

PubMed1989

Distribution of dopamine D1 and D2 receptors in rabbit cortical areas, hippocampus, and neostriatum in relation to dopamine contents.

The densities of dopamine D1 and D2 receptors were measured by using [3H]SCH23390 and [3H]raclopride, respectively, in the rabbit cingulate, visual, sensorimotor, and entorhinal-piriform cortical areas; the dorsal and ventral hippocampus; and the putamen as well as the medial and lateral caudate. Endogenous dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), 4-hydroxy-3-methoxyphenylacetic acid (HVA), and 3-methoxytyramine (3-MT) were assayed by HPLC with electrochemical detection. The distributions of [3H]SCH23390 and [3H]raclopride binding were heterogenous with the greatest densities in the neostriatum. The concentrations of DA and its metabolites were also highest in this structure. Regions with low DA content, i.e., cortex and hippocampus, had lower densities of [3H]SCH23390 and [3H]raclopride binding. Furthermore, these sites were differentially localized within the various regions and there were substantially more D1 than D2 receptors. The functional significance and heterogeneities in the distribution of D1 and D2 receptors are discussed in relation to the dopaminergic innervation and the turnover estimated by the ratios between endogenous DA and its metabolites.

Animals↗

PubMed1989

Dopamine D1 receptors labelled with [3H]SCH23390 in rabbit cerebral cortex and neostriatum. Equilibrium binding, kinetics and selectivity.

The binding characteristics of the novel benzazepine compound SCH23390 were studied using membrane preparations from rabbit cerebral cortex (CTX) and neostriatum (CPU; caudate putamen). The association kinetics of [3H]SCH23390 to membranes from CTX and CPU were rapid, while the dissociation kinetics were extremely slow and only around 40-60% of the binding was displaced two hours after the addition of either S(+)-butaclamol or 30 volumes of buffer. The saturation curves revealed that [3H]SCH23390 bound with high affinity in both tissues, with densities of 133 fmol/mg protein for CTX (Kd 25 degrees C = 0.31 nM) and 664 fmol/mg protein for CPU (Kd = 0.13 nM). the specificity of binding to the cortical D1 receptor was verified in competition experiments with a variety of dopaminergic agents. The rank order of potency of these compounds was consistent with the pharmacology of the dopaminergic D1 site. All competition curves were better fitted to a one-site model with Hill coefficients around one, indicating that [3H]SCH23390 was binding to a single cortical site. The stereoselectivity of the cortical [3H]SCH23390 binding site could be demonstrated by the use of enantiomer pairs of dopaminergic drugs. This study provides compelling evidence that [3H]SCH23390 binds to dopamine D1 receptors in the neostriatum and cerebral cortex of the rabbit.

Animals↗

PubMed1989

Monoamines and metabolites in autopsied brain tissue from cirrhotic patients with hepatic encephalopathy.

Alterations in the metabolism of monoamine neurotransmitters have been proposed to be involved in the development of the hepatic encephalopathy (HE) associated with experimental and human liver failure. In order to evaluate this hypothesis, the monoamines and some of their metabolites were measured in homogenates of caudate nucleus (CAU), prefrontal (PFCo) and frontal cortex (FCo) dissected from brains obtained at autopsy from nine cirrhotic patients who had died in hepatic coma and an equal number of control subjects, free from neurological, psychiatric and hepatic disorders, matched for age and time interval from death to freezing of autopsied brain samples. Monoamine measurements were performed by high-performance liquid chromatography with ion-pairing and electrochemical detection after a simple extraction procedure. In all three regions investigated, concentrations of dopamine (DA) were unchanged in cirrhotic patients vs controls while its metabolites, 3-methoxytyramine (3-MT) and homovanillic acid (HVA) were selectively affected i.e. 3-MT was found to be increased in CAU, while HVA levels were increased in FCo and CAU. DOPAC was also found to be unchanged in CAU. Noradrenaline (NA) levels were greatly increased in PFCo and FCo of cirrhotic patients but remained unchanged in CAU. No significant differences in the concentrations of either serotonin (5-HT) or of its precursor 5-hydroxytryptophan (5-HTP) were found in any of the three regions studied. However, 5-hydroxyindoleacetic acid (5-HIAA), the major metabolite of 5-HT, was increased in PFCo and CAU of cirrhotic patients. These findings show that selective alterations of catecholamine and 5-HT systems are involved in human HE and therefore, they may play an important role in the pathogenesis of certain neurological symptoms associated with this encephalopathy.

Aged↗

PubMed1989

Effects of sodium, lithium, and magnesium on in vitro binding of [3H]SCH23390 in rat neostriatum and cerebral cortex.

The effects of sodium, lithium, and magnesium on the in vitro binding properties of the D1 antagonist [3H]SCH23390 were examined with membrane preparations from rat neostriatum (CPU; caudate-putamen) and cerebral cortex (CTX). The saturation binding isotherms for both tissues performed in the presence of 120 mM of either Na+ or Li+ revealed an increase in the affinity, as compared to that observed when the incubation buffer was composed of Tris-Cl 50 mM with MgCl2 1 mM alone. For the CPU there were no changes in the maximum binding capacity (Bmax) in the different buffers used. In the case of the CTX, there was a loss of [3H]SCH23390 binding sites when either Na+ or Li+ 120 mM were added to the incubations, suggesting a lack of selectivity of this ligand in the absence of group IA cations. The agonist state of the [3H]SCH23390 binding site was studied in competition experiments with dopamine. The highest agonist affinity was obtained in 50 mM Tris-Cl buffer with 1 mM MgCl2 while the addition of 120 mM of either Na+ or Li+ caused a 3- to 5-fold decrease in the potency of dopamine to compete with specific [3H]SCH23390 binding in both CPU and CTX. The presence of magnesium was essential for the competition experiments; i.e.: a concentration of 1 mM MgCl2 was optimum to obtain dopamine antagonism of ligand binding, while increasing Mg2+ to 2 or 5 mM did not appear to further improve the inhibitions. The results support both agonist and antagonist affinity shifts for the dopamine D1 receptor labeled with [3H]SCH23390.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Endogenous homovanillic acid levels differ between rat and rabbit caudate, hippocampus, and cortical regions.

Endogenous dopamine (DA) levels and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3MT) and homovanillic acid (HVA) were measured by high-performance liquid chromatography in the entorhinal-piriform (EnPi), cingulate (CIN), sensorimotor (SSM) and visual (VIS) cortices as well as is the caudate (CAU) and hippocampus (HIP) of Sprague-Dawley (SD) rats and New Zealand (NZ) rabbits. The DA, DOPAC and 3MT contents were similar in both species. The HVA levels however, although they followed DA distribution, were several-fold higher in NZ rabbits than in SD rats for all cortices, HIP and CAU. In addition, total metabolite contents and DA turnover (estimated from 'DA metabolite/DA' ratios) were significantly higher in NZ rabbits than in SD rats, suggesting an increased release and/or metabolism in the former species. The HVA/DA ratios were much higher for NZ rabbit regions than for SD rats, indicating an increased DA release in the former species since the DOPAC/DA ratios (index of intraneuronal degradation) were similar.

Animals↗

PubMed1989

Distribution of monoamines and metabolites in rabbit neostriatum, hippocampus and cortex.

The monoamines noradrenaline (NA), dopamine (DA), adrenaline (AD) and 5-hydroxytryptamine (5-HT) were assayed in the putamen (PUT), the lateral (lCAU) and medial (mCAU) portions of the caudate, the dorsal (dHIP) and ventral (vHIP) hippocampus, as well as in four cortical areas, i.e., anterior cingulate (CIN), entorhinal-piriform (EnPi), sensorimotor (SSC; somatosensory) and primary visual (VIS). The use of an HPLC procedure enabled us to perform these measurements in microdissected samples and to assay as well monoamine metabolites. The DA levels were highest in the neostriatum, moderate in the EnPi and CIN and very low in the SSC, VIS and hippocampus. The distribution of NA was more uniform, although higher concentrations were measured in the neostriatum, hippocampus and EnPi. The largest amounts of 5-HT were in the EnPi, while moderate concentrations were found in the other regions. The ratios between the neurotransmitters and their metabolites were used as an index of turnover and indicate that the terminal fields of the monoamine systems are heterogenous within the neostriatal, hippocampal and cortical subdivisions.

Animals↗

PubMed1989

Specific [3H]SCH23390 binding to dopamine D1 receptors in cerebral cortex and neostriatum: role of disulfide and sulfhydryl groups.

Receptor binding studies were performed in cerebral cortex (CTX) and neostriatum (CPU; caudate-putamen) using the dopamine D1 antagonist [3H]SCH23390. Because receptors are of protein nature, we examined the role of disulfide bonds (--SS--) and sulfhydryl groups (--SH) in the specific binding of [3H]SCH23390. Furthermore, membrane preparations contain a certain amount of lipid, so that treatments with --SH and --SS-- reagents could determine whether the fixation of the radioligand was to protein or to the lipid moiety. Pretreatment of CTX and CPU membranes with dithioerythritol, L-dithiothreitol, or 5,5'-dithiobis(2-nitrobenzoic acid), as well as with the alkylating agent N-ethylmaleimide, produced dose-dependent decreases of specific [3H]SCH23390 binding in membrane preparations from both tissues. These changes were not reversible after up to two washes, but could be prevented in part if the treatments were performed in the presence of dopamine. Additional protection experiments were conducted with (+)- and (-)-butaclamol, as well as with (+)- and (-)-SKF38393. A series of saturation experiments (with pretreated membranes in the absence of reactives) demonstrated that the alkylation of --SS-- groups reduced specific [3H]SCH23390 binding mainly through an affinity change, but L-dithiothreitol and 5,5-dithiobis(2-nitrobenzoic acid) decreased the number of binding sites. The affinity of the receptor to agonists was examined with the two enantiomers of SKF38393; the inhibition curves showed that residual binding was not affected and stereospecificity was conserved. The present results provide evidence for the participation of both --SS-- and --SH groups in the recognition site of the dopamine D1 receptor in both the CTX and the CPU.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1989

Modulatory effects of catecholamines on neurons of the rat visual cortex: single-cell iontophoretic studies.

The catecholamines noradrenaline and dopamine have been proposed as neuromodulators of cortical neuron excitability, and such a regulation could be mediated by specific adrenergic and dopaminergic receptors. We characterized electrophysiologically some of the types of responses to the iontophoretic application of adrenergic and dopaminergic agonists and antagonists on single cells in the rat visual cortex (areas occipital 1 monocular or Oc1M and occipital 1 binocular or Oc1B). For the majority of spontaneously active and visual cortical cells, noradrenaline and dopamine decreased the firing frequency. In the case of visually driven (synaptically activated) neurons, background firing was the main component of the response to be inhibited by the administration of noradrenaline, clonidine, and oxymetazoline, leading to an enhancement of the signal-to-noise ratio. Since these effects could be reduced or blocked by a previous ejection of the specific alpha 2-antagonist idazoxan, the findings support a role for alpha 2-adrenergic receptors in the transmission of sensory inputs to the visual cortex. These effects were not found with the mixed alpha-adrenergic agonist phenylephrine nor with the beta-agonist isoproterenol. Finally, the use of the inhibitory amino acid GABA rules out a simple hyperpolarizing response as the mechanism underlying noradrenaline modulatory effects in the cerebral cortex.

Adrenergic alpha-Agonists↗

PubMed1989

Dopamine D2 receptors labeled with [3H]raclopride in rat and rabbit brains. Equilibrium binding, kinetics, distribution and selectivity.

The binding properties of the substituted benzamide raclopride to dopamine D2 receptors were studied with membrane preparations from rat and rabbit neostriatum. An analysis of the association kinetics suggested a single binding site but the data from the dissociation experiments were better described by a two-site model. Examination of saturation curves at equilibrium revealed a single class of binding sites in the neostriatum from both species (rat: maximum binding capacity (Bmax) = 247 fmol/mg of protein; rabbit: Bmax = 337 fmol/mg of protein). In cortical regions known to possess a distinct dopaminergic innervation (piriform-entorhinal areas and cingulate cortex) the Bmax values ranged between 9 and 22 fmol/mg of protein. [3H]Raclopride binding sites (less than 12 fmol/mg of protein) were also detectable in the dorsal and ventral hippocampus as well as in the somatosensory and visual cortices. The selectivity in the neostriatum was examined by competition experiments with dopaminergic drugs. The rank of potency of agonists and antagonists to displace [3H]raclopride binding revealed its selectivity for the dopamine D2 receptor and was essentially the same for both species. Antagonist competition curves could be fitted to a single site but inhibition by agonists was better described assuming a two-site model. The stereospecificity of binding was demonstrated by the use of the enantiomer pairs. These results validate the utilization of the novel benzamide [3H]raclopride as a selective marker of dopamine D2 receptors.

Animals↗

PubMed1988

Distribution of dopamine D1 receptors in rat cortical areas, neostriatum, olfactory bulb and hippocampus in relation to endogenous dopamine contents.

The tritiated dopamine D1 antagonist SCH23390 was employed to determine the densities of D1 receptors in seven discrete and functionally identified cortical areas (cingulate, frontal, parietal, primary somatosensory, primary visual, retrosplenial and entorhinal-piriform) as well as in the neostriatum, hippocampus and olfactory bulbs. In addition, the tissue levels of the catecholamines NA, AD, DA, the indoleamine 5-HT and their main metabolites (MHPG, DOPAC, HVA, 3-MT, 5-HTP and 5-HIAA) were measured in the different regions by HPLC with electrochemical detection. The Scatchard analysis of saturation curves revealed the highest density of [3H]SCH23390 binding sites for the neostriatum, while the densities were 10-20 times lower for total cerebral cortex and hippocampus respectively. For the olfactory bulb and other cortical areas, D1 receptor densities were determined by equilibrium binding at a fixed radioligand concentration approaching saturation. The distribution of D1 receptors was heterogeneous with the greatest densities in entorhinal-piriform and cingulate cortices. The endogenous DA levels measured for all regions correlated with their metabolite (DOPAC, HVA and 3-MT) contents (r = 0.999; P less than 0.001). There was also a very good correlation (r = 0.981; P less than 0.001) between tissue DA and D1 receptor densities. This quantitative information reflects particular features of the organization of the DA systems and is discussed in relation to turnover and recently established aspects of the DA innervation.

Animals↗

PubMed1988

Acute effects of lithium on dopaminergic responses: iontophoretic studies in the rat visual cortex.

The interactions between lithium and cortical dopaminergic receptors were investigated using the iontophoretic technique to record and apply dopaminergic compounds, GABA, acetylcholine and LiCl on neurons in the primary visual cortex of the rat. The main responses to dopamine (DA) or to the D1 agonist (+/- )SKF38393 on spontaneously-active (SA) or visually-driven (VD) units was a prolonged decrease in firing and a reduction in the responsiveness to pulses of acetylcholine. The D1 antagonist SCH23390, applied iontophoretically or intravenously, blocked or attenuated the inhibitory responses to both DA and (+/- )SKF38393. The D2 agonist quinpirole (LY171555) either produced only slight excitations or had no effects on both VD and SA units. The concomitant application of lithium blocked the inhibitory responses to DA and to (+/- )SKF38393 but did not modify the responsiveness to LY171555. In addition, the DA- and (+/- )SKF38393-induced decreases in responsiveness to acetylcholine were also suppressed by lithium. These effects were on dopaminergic mechanisms, since the excitatory responses to acetylcholine alone as well as the inhibitions caused by GABA were unchanged by the application of lithium. These results imply that the modifications in sensitivity to dopaminergic agents induced by lithium are mediated by dopamine D1 receptors and are discussed in relation to adenylate-cyclase.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1988

Effects of alpha-methyl-p-tyrosine on monoamines and catecholamine receptors in rat cerebral cortex and neostriatum.

The effects of inhibiting the synthesis of catecholamines using alpha-methyl-p-tyrosine (alpha-MPT) were investigated in four cortical regions (cingulate, somatosensory, visual and entorhinal-piriform) as well as in the neostriatum (caudate-putamen). After acute (48 hours) treatments with alpha-MPT the endogenous NA levels were significantly reduced in all regions examined. The DA contents were also decreased in regions known to possess a dense dopaminergic innervation (neostriatum, cingulate and entorhinal-piriform cortices) but not in the somatosensory and visual areas, where DA is normally present in small amounts. Serotonin and 5-HIAA levels were either unaffected or increased. After such catecholamine synthesis inhibitions, there were no changes in the binding parameters (Bmax and Kd) of [3H]prazosin (alpha 1-receptors), [3H]idazoxan (alpha 2-receptors), [3H]dihydroalprenolol (total beta receptors) in the cerebral cortex nor in [3H]SCH23390 sites (dopamine D1 receptors) in both cerebral cortex and neostriatum. The results indicate that acute catecholamine depletions but with conservation of the fibers do not produce receptor modifications.

Animals↗

PubMed1988

Specific [3H]SCH23390 binding to dopamine D1 receptors in cerebral cortex and neostriatum: evidence for heterogeneities in affinity states and cortical distribution.

The tritiated antagonist SCH23390 was used to identify dopamine D1 receptors in the cerebral cortex and neostriatum. The kinetic properties of binding were investigated in parallel experiments with membrane preparations from both tissues. The densities of receptors (Bmax) and the dissociation constants (KD) were determined from saturation curves, and the specificity of binding verified in competition experiments using agonists and antagonists. The cortical D1 receptor displays the same pharmacological selectivity (including stereospecificity) and kinetic properties as the neostriatal D1 receptor. From both the dissociation kinetics by dilution and the competition curves, it could be established that there is an heterogeneity of binding probably due to high- and low-affinity states. Endogenous dopamine, 4-hydroxy-3-methoxyphenylacetic acid, 3,4-dihydroxyphenylacetic acid, and 3-methoxytyramine contents, as well as D1 receptor distribution, were measured for the neostriatum and four localized cortical areas: anterior cingulate, primary somatosensory, primary visual, and piriform-entorhinal. For the regions examined, the distribution of D1 receptors is heterogeneous, but correlates very well (r greater than 0.98) with the endogenous levels of dopamine and its major metabolites.

Animals↗

PubMed1987

Noradrenergic effects on rat visual cortex: single-cell microiontophoretic studies of alpha-2 adrenergic receptors.

The catecholamine noradrenaline has been proposed to modulate the excitability of cortical neurons, and such a regulation may be mediated by specific adrenergic receptors. We characterized, using electrophysiological recordings, the types of responses of single cells in the rat visual cortex (areas 17 and 18) to the iontophoretic application of adrenergic agents. For the majority of spontaneous and visually-driven cells sampled, noradrenaline decreased the firing frequency, and in some cases of visually-driven cells could increase the signal/noise ratio. These effects were also documented after the application of the alpha-2 adrenergic agonists clonidine and oxymetazoline, and could be reduced or blocked by a previous ejection of the specific alpha-2 antagonist idazoxan. The present study supports a role for alpha-2 adrenoceptors in the modulation of sensory inputs to the visual cortex.

Adrenergic alpha-Agonists↗

PubMed1987

Adrenergic receptor and catecholamine distribution in rat cerebral cortex: binding studies with [3H]prazosin, [3H]idazoxan and [3H]dihydroalprenolol.

The tritiated adrenergic antagonists [3H]dihydroalprenolol ([3H]DHA; beta-receptors), [3H]prazosin ([3H]PRZ; alpha 1-receptors), and [3H]idazoxan ([3H]IDA; alpha 2-receptors) were used to determine the distribution of these sites in 5 defined areas of the adult rat cerebral cortex. The highest density of [3H]PRZ binding was found in the prefrontal cortex, with a lower and homogeneous distribution for the frontal, parietal, occipital and temporal areas. The [3H]IDA binding sites were fairly uniform for all areas, except for the temporal cortex where it was very dense. In contrast, beta-adrenoceptors labelled by [3H]DHA were very homogeneous for all the regions examined. The functional significance of the distribution of alpha 1, alpha 2 and beta-adrenoceptors is discussed in relation to the catecholamine innervation and monoamine contents measured by high performance liquid chromatography.

Alprenolol↗

PubMed1987

Distribution of catecholamines, serotonin, and their major metabolites in the rat cingulate, piriform-entorhinal, somatosensory, and visual cortex: a biochemical survey using high-performance liquid chromatography.

The catecholamines noradrenaline (NA), dopamine (DA), adrenaline (AD), the indoleamine 5-hydroxytryptamine (5-HT; serotonin), as well as some of their major metabolites were assayed by high-performance liquid chromatography (HPLC) with electrochemical detection, in four well-defined areas of the rat cerebral cortex: anterior cingulate (CIN;Cg1 and Cg3), piriform and entorhinal (PiEn), hind-limb primary somatosensory (SSC;HL) and primary visual (VIS; Oc1M and Oc1B). The concentrations of NA and that of its main metabolite 3-methoxy-4-hydroxyphenylglycol were highest in PiEn, had intermediate values in CIN and were lowest for SSC and VIS cortices. The DA levels were also highest in PiEn, intermediate in CIN, while the lowest values were in SSC and VIS cortices. The different DA/NA ratios support the hypothesis that they are indeed independent neurotransmitters. In addition, the levels of 3,4-dihydroxyphenylacetic acid, homovanillic acid and 3-methoxytyramine paralleled the distribution of DA, thus confirming the presence of release sites, even in regions in which the low levels of this catecholamine could be interpreted simply as the precursor of NA. Traces of AD were detected in all the regions examined. The 5-HT contents, as well as that of its precursor 5-hydroxy-1-tryptophan and that of its metabolite 5-hydroxyindole-3-acetic acid were also found to be non-homogenous, with the highest levels measured in the PiEn and CIN regions.

3,4-Dihydroxyphenylacetic Acid↗