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T A Reader

Publications and source records attributed to T A Reader.

At least 37 records · Page 2Linked to original sources
PubMed1999

Serotonin innervation of Lurcher mutant mice: basic data and manipulation with a combination of amantadine, thiamine and L-tryptophan.

The Lurcher (Lc/+) mutant mouse is characterized by a considerable atrophy of the cerebellum due to a massive loss of cerebellar Purkinje and granule cells, as well as of neurons from the inferior olivary nucleus. In this study the effects of a therapeutic combination of amantadine, thiamine and L-tryptophan on the serotonin (5-HT) innervation was assessed in Lurcher mice by autoradiography, using [3H]citalopram to label 5-HT transporters. In wild type mice as well as in both saline-treated and drug-treated Lurcher mutants, [3H]citalopram binding remained unchanged in forebrain and brainstem regions. In the cerebellum, labelling of deep cerebellar nuclei (CBnuc) was about twofold higher than in the cortex (CBctx). In saline-treated Lurcher mutants compared to wild type mice, the densities of [3H]citalopram were 98% higher in CBctx, and 180% higher in CBnuc. In CBctx of drug-treated Lurcher mutants, transporter densities were 89% higher than in the wild type, but did not differ from the saline-treated Lurcher. In the CBnuc of the drug-treated Lurcher mutants, [3H]citalopram binding was 50% higher than in the saline-treated Lurcher group, and 320% higher than in wild type mice. The results show that 5-HT transporters, already upregulated in the CBnuc of Lurcher mutant mice, can be further increased by a pharmacological treatment, possibly altering the availability of 5-HT in some of its target areas.

5-Hydroxytryptophan↗
PubMed1999

Effects of antipsychotic drugs on dopamine and serotonin contents and metabolites, dopamine and serotonin transporters, and serotonin1A receptors.

The effects of neuroleptics have been attributed to dopamine (DA) receptor blockade; however, other neurotransmitters, in particular serotonin (5-HT), have also been implicated. In this study, we examined the effects of clozapine and haloperidol on the distribution of DA and 5-HT transporters, on endogenous DA, 5-HT and their major metabolites, and on 5-HT1A receptors. Adult male Sprague-Dawley rats were treated with either haloperidol (1 mg/kg/day, i.p.), clozapine (20 mg/kg/day, i.p.) or saline for 21 days, and following 3 days of withdrawal, the brains were removed. Tissue levels of DA and 5-HT and their metabolites were measured by high-performance liquid chromatography in 16 brain regions, while quantitative autoradiography with [125I]RTI-121, [3H]citalopram and [3H]8-OH-DPAT was employed to label DA transporters, 5-HT transporters and 5-HT1A receptors, respectively. After haloperidol, densities of 5-HT transporters were increased in the dorsal insular cortex and in the ventral half of caudal neostriatum, while 5-HT1A receptors augmented in cingulate cortex but decreased in the entorhinal area. After clozapine, [3H]citalopram labelling was increased in ventral hippocampus, ventral caudal neostriatum and nucleus raphe dorsalis, but decreased in medio-dorsal and latero-dorsal neostriatum as well as in substantia nigra. Binding of [3H]8-OH-DPAT following clozapine was decreased in frontal, parietal, temporal and entorhinal cortices but increased in the CA3 division of Ammon's horn. The changes in 5-HT transporters in nucleus raphe dorsalis and substantia nigra, as well as the 5-HT1A receptor down-regulations caused by clozapine but not by haloperidol, may explain effects obtained with clozapine and other atypical neuroleptics. There were no modifications in densities of DA transporters, nor of tissue DA levels, after the chronic neuroleptic treatments. The results are in line with previous suggestions that a certain degree of tolerance to neuroleptics develops, in spite of profound D1 and D2 receptor changes that persist during the entire chronic treatment with these psychotropic agents.

Animals↗
PubMed1999

Effects of denervation and hyperinnervation on dopamine and serotonin systems in the rat neostriatum: implications for human Parkinson's disease.

The research on central synaptic neurotransmission has greatly benefited from the use of the neurotoxin 2,4,5-trihydroxyphenylethylamine, or 6-hydroxydopamine (6-OHDA), that destroys catecholamine-containing neuronal cell bodies and nerve terminals. Refinements in the use of this neurotoxin led to the use of dopamine-denervated animals as models of human Parkinson's disease, in which the loss of dopaminergic neurons is a prominent feature. Here we review structural, pharmacological, and biochemical studies carried out in the adult and neonatal 6-OHDA lesioned animals. These models have become useful and interesting paradigms to examine alterations in the expression of receptors and in their sensitivity to agonist drugs; some of these modifications may underlie the altered responsiveness of the dopamine-lesioned animals to dopamine, but also to other compounds, including serotoninergic drugs. We have also reviewed studies of amino acids as well as of monoamine metabolism and of uptake mechanisms that may underlie some of the behavioural alterations in these models that have become relevant for our understanding of the sprouting and plastic properties of spared neurons, and of the alternate neuronal projections that replace lesioned terminals, enabling compensatory adaptations. Although 6-OHDA-lesioned animals, that display some biochemical characteristics of Parkinson's disease in humans, do not express all of the neurological features exhibited by patients, the increasing knowledge that can be obtained from studies in simplified experimental models will undoubtedly lead to the development of innovative drugs and other replacement therapies for degenerative brain diseases.

Animals↗
PubMed1999

Regional brain distribution of noradrenaline uptake sites, and of alpha1-alpha2- and beta-adrenergic receptors in PCD mutant mice: a quantitative autoradiographic study.

The mouse "Purkinje cell degeneration" (pcd) is characterized by a primary loss of Purkinje cells, as well as by retrograde and secondary partial degeneration of cerebellar granule cells and inferior olivary neurons; this neurological mutant can be considered as an animal model of human degenerative ataxia. To determine the consequences of this cerebellar pathology on the noradrenergic system, noradrenaline transporters as well as alpha1-, alpha2- and beta-adrenergic receptors were evaluated by quantitative ligand binding autoradiography in adult control and pcd mice using, respectively, [3H]nisoxetine, [3H]prazosin, [3H]idazoxan and [3H]CGP12177. In cerebellar cortex and deep nuclei of pcd mutants, [3H]nisoxetine labelling of noradrenaline transporters was higher than in control mice. However, when binding densities were corrected by surface area, they remained unchanged in the cerebellar cortex but associated with 25% and 40% lower levels of labelling of alpha1 and beta receptors, as well as a very important increase (275%) of alpha2 receptors. In deep cerebellar nuclei, surface corrections did not reveal any changes either in transporter or in receptor densities. Higher densities of [3H]nisoxetine labelling were found in several regions related with the cerebellum, namely inferior olive, inferior colliculus, vestibular, reticular, pontine, raphe and red nuclei, as well as in primary motor and sensory cerebral cortex; they may reflect an increased noradrenergic innervation related to motor adjustments for the cerebellar dysfunction. Increased [3H]nisoxetine labelling was also measured in vegetative brainstem regions and in dorsal hypothalamus, implying altered autonomic functions and possible compensation in pcd mutants. Other changes found in extracerebellar regions affected by the mutation, such as thalamus and the olfactory system implicated both noradrenaline transporters and adrenergic receptors. In contrast to the important alterations of the noradrenergic system in cerebellar cortex, the lack of receptor changes in deep cerebellar nuclei suggests that local adaptations may be sufficient to minimize the consequence of the cerebellar atrophy on motor control. An intense labelling by [3H]idazoxan of the inner third of the molecular layer was a novel, albeit unexplained finding, and could represent a postsynaptic subset of alpha2-adrenergic receptors.

Adrenergic alpha-Antagonists↗
PubMed1999

Effects of L-tryptophan on indoleamines and catecholamines in discrete brain regions of wild type and Lurcher mutant mice.

The biochemical parameters of the serotoninergic system were examined in wild type mice and Lurcher mutants after chronic treatment (40 days) with the serotonin (5-HT) precursor L-tryptophan (50 mg/kg; i.p.). Tissue contents in 5-HT, dopamine and noradrenaline, as well as some of their metabolites, were measured in frontal cortex, neostriatum, thalamus, brainstem, cerebellum and spinal cord by high-performance liquid chromatography. The tissue levels were used as a biochemical index of the function of the monoamine innervations in this animal model of cerebellar ataxia. The results show that Lurcher mutants retain higher concentrations of L-tryptophan and total indoleamines, but that 5-HT is probably stored in a non-releasable compartment. In the particular case of the hypoplastic cerebellum, the reorganization of 5-HT nerve terminals leads to an accrued indoleamine synthesis, indicating that the Lurcher mutants can accumulate 5-HT, but do not utilize it efficiently in synaptic transmission.

Animals↗
PubMed1999

Distribution of dopamine, its metabolites, and D1 and D2 receptors in heterozygous and homozygous weaver mutant mice.

In weaver mice, besides a postnatal cerebellar developmental anomaly probably caused by alterations of an inwardly rectifying K+ channel, there is a progressive loss of mesencephalic dopaminergic neurons. To further evaluate this deficit, endogenous dopamine and its metabolites were measured in 22 brain regions from heterozygous (wv/+) and homozygous (wv/wv) mutants, and compared to wild type (+/+) mice. In both wv/+ and wv/wv mutants there were profound dopamine depletions in all regions; these changes were accompanied by decreases in metabolites but with an increase of turnover indexes. Dopamine D1 and D2 receptors were examined by autoradiography, and their distribution was conserved. The results show that the dopaminergic deficit is widespread to all areas of innervation, and is probably compensated for by an increased turnover. Abnormal developmental growth signals, or aberrant cellular responses, may result in defective neurite formation of the midbrain dopaminergic neurons, leading to their postnatal death.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

Pharmacological activation and modulation of the central pattern generator for locomotion in the cat.

Pharmacological agents have been shown to be capable of inducing a pattern of rhythmic activity recorded in muscle nerves or motoneurons of paralyzed spinal cats that closely resembles the locomotor pattern seen in intact cats. Further work, using intraperitoneal or intrathecal injections, suggests that different neurotransmitters may be involved in various aspects of locomotor control, e.g., initiation and modulation of the pattern. Although precursors, agonists or the neurotransmitters themselves of several systems have been investigated (noradrenergic, dopaminergic, serotonergic, glutamatergic), the noradrenergic system seems the most efficient in triggering locomotion in complete spinal cats, with the alpha-2 agonists (clonidine, tizanidine, oxymetazoline) being more potent than the alpha-1 agonist, methoxamine. Moreover, the potency of the drugs may depend on the time of application after the spinal lesion. In chronic spinal cats capable of spontaneous walking on hindlimbs on the treadmill, all neurotransmitters appear to exert distinct recognizable effects on the locomotor pattern. More recent work also suggests that the effects of drugs may differ significantly depending on the type of spinal lesion. For instance, clonidine further reduces the level of weight support during quadrupedal locomotion of cats with lesions of the ventral-ventrolateral funiculi, possibly due to an interference of clonidine with essential compensatory mechanisms used by these animals to walk. Such considerations as the type of drugs, type of lesions, and the time after the lesion will be important for future studies in spinal cord injured patients.

5-Hydroxytryptophan↗
PubMed1998

Functional evidence that BDNF is an anterograde neuronal trophic factor in the CNS.

In this report, we have tested the hypothesis that brain-derived neurotrophic factor (BDNF) is an anterograde neurotrophic factor in the CNS and have focused on central noradrenergic neurons that synthesize BDNF. Double-label immunocytochemistry for BDNF and dopamine-beta-hydroxylase (DBH), a marker for noradrenergic neurons, demonstrated that BDNF is partially localized to noradrenergic nerve fibers and terminals in the adult rat brain. To test the functional importance of this anterograde BDNF, we analyzed transgenic mice carrying a DBH-BDNF minigene. Increased synthesis of BDNF in noradrenergic neurons of DBH-BDNF mice caused elevated TrkB tyrosine kinase activation throughout postnatal life in the neocortex, a noradrenergic target region. This afferently regulated increase in TrkB receptor activity led to long-lasting alterations in cortical morphology. To determine whether noradrenergic neuron-expressed BDNF also anterogradely regulated neuronal survival, we examined a second noradrenergic target, neonatal facial motoneurons. One week after axotomy, 72% of facial motoneurons were lost in control animals, whereas only 30-35% were lost in DBH-BDNF transgenic mice. Altogether, these results indicate that BDNF is anterogradely transported to fibers and terminals of noradrenergic neurons, that anterogradely secreted BDNF causes activation of TrkB in target regions, and that this secretion has functional consequences for target neuron survival and differentiation. This presynaptic secretion of BDNF may provide a cellular mechanism for modulating neural circuitry, in either the developing or mature nervous system.

Age Factors↗
PubMed1998

Brain dopamine and amino acid concentrations in Lurcher mutant mice.

Lurcher mutant mice are characterized by massive degeneration of the cerebellum, including Purkinje cells and granule cells, as well as for the loss of neurons from the inferior olive. Concentrations of dopamine and two of its metabolites and of several amino acid neurotransmitters were determined in the cerebellum and in other brain regions of these mutants. By comparison to wild-type mice of the same background strain, glutamate and taurine concentrations were reduced in the Lurcher cerebellum. No decrease was found for aspartate, gamma-aminobutyric acid (GABA), glycine, as well as dopamine and its metabolites. Moreover, no neurochemical alterations occurred in the brain stem, thalamus, or neostriatum of Lurcher mutants. A selective reduction of glutamate concentration was found in the hippocampus, while all amino acids measured were decreased in the entorhinal-piriform areas. These results indicate region-selective reductions of neurotransmitter concentrations in a mouse mutant with a defined cerebellar cortical pathology.

Amino Acids↗
PubMed1998

Distribution of dopamine transporters in basal ganglia of cerebellar ataxic mice by [125I]RTI-121 quantitative autoradiography.

Dopamine (DA) uptake sites, or transporters, were examined with [125I]RTI-121 in mutant mice that exhibit motor control deficits, namely weaver, lurcher and dystonia musculorum. In lurcher mice, the distribution of [125I]RTI-121 binding was similar to controls, except for a decrease in the subthalamic nucleus. For dystonia musculorum mice, the labelling presented no differences between controls and mutants, except for decreases in the dorsal half of caudal neostriatum and in the ventral tegmental area. Moreover, in this mutant the left rostral neostriatum DA transporters were reduced, when compared to the right counterpart. In weaver heterozygote (wv/+) mice, the distribution and density gradients of [125I]RTI-121 labelling were similar as in their controls, except in caudal neostriatum, where binding was slightly higher. In contrast, the weaver homozygote (wv/wv) showed important decreases in labelling of the dorsal quadrant of rostral neostriatum as well as of the dorsal half of caudal neostriatum, where the reductions of binding densities were of 65% to 70%, respectively. There were also slight decreases in [125I]RTI-121 binding in olfactory tubercles as well as in subthalamic nucleus, but only in wv/wv mice. In substantia nigra pars compacta and ventral tegmental area of wv/wv mice the labelling was lower; however, while the 60% decrease in labelling in substantia nigra was highly significant, the 30% reduction in ventral tegmental area did not attain statistical significance. In summary, in the ataxic neurological mutant mice studied, important reductions of DA transporters were documented only for the weaver mice, the cerebellar mutant presenting, besides its cerebellar pathology, a known degeneration of mesencephalic dopaminergic neurons. The results rule out major alterations of the central DA systems in lurcher and dystonia musculorum, and are compatible with the hypothesis that the dopaminergic abnormalities of weaver mutants are not secondary to cerebellar atrophy, but may be a direct consequence of the abnormal weaver gene expressed by DA neurons leading to their apoptotic death.

Animals↗
PubMed1998

The treatment of spinocerebellar ataxias: facts and hypotheses.

Actual therapeutic assays in spinocerebellar ataxias, i.e. in Friedreich's ataxia (FA) and olivopontocerebellar atrophy (OPCA) are discussed in relation to (i) the serotoninergic theory; (ii) the excitotoxic action of glutamate; and (iii) cerebrospinal fluid thiamine deficiency in ataxic patients. Data from the literature show that neurochemical deficiencies arising from cerebellar damage in both FA and OPCA patients are multiple. Assays of replacement and neuroprotective therapeutics with a single drug have produced controversial data or mildly effective results. Consequently, it is hypothesized that a drug cocktail, i.e. L-5-hydroxytryptophan, thiamine and amantadine hydrochloride, would be more beneficial. This cocktail proved to be useful in open studies, improving respiratory disorders in FA patients. More powerful inhibitors of N-methyl-D aspartate receptor channels should be tried initially in animal experiments.

Animals↗
PubMed1998

Regional distribution of 5-HT transporters in the brain of wild type and 'Purkinje cell degeneration' mutant mice: a quantitative autoradiographic study with [3H]citalopram.

The neurological mutant 'Purkinje cell degeneration' (pcd) is characterized by a primary degeneration of Purkinje cells, as well as by retrograde and secondary partial degeneration of cerebellar granule cells and inferior olivary neurons, and can be considered as an animal model of human degenerative ataxias. The serotonin (5-HT) innervation was examined in wild type and pcd mice, by quantifying 5-HT uptake sites, or transporters, using [3H]citalopram binding autoradiography. In both wild type and pcd mutants, the highest densities of 5-HT transporters were in mesencephalic and rostral pontine regions, in limbic structures, in hypothalamus and in discrete thalamic divisions, while the lowest labelling was found in cerebellum and brainstem reticular formation. In pcd mice, although [3H]citalopram labelling was higher in cerebellar cortex and deep cerebellar nuclei, when binding densities were corrected for surface area, the up-regulation of 5-HT transporters was present only in deep cerebellar nuclei. Also, higher labelling was found in nuclei raphe dorsalis and medialis, in ventral divisions of rostral neostriatum, caudal neostriatum, rostral globus pallidus, posteromedial amygdaloid nucleus, septum, olfactory tubercles, vertical limb of Broca's diagonal band, periventricular, latero-ventral and medio-ventral thalamic nuclei, medial geniculate nucleus, anterior hypothalamus and entorhinal cortex. The results indicate a relative integrity of the 5-HT innervation, but with a reorganization of serotoninergic terminals in the cerebellum, in particular in the deep cerebellar nuclei. This suggests that in progressive cerebellar degeneration, as found in the pcd mutant, the modified 5-HT system may still participate in motor functions by exerting an overall modulation of excitatory amino acid neurotransmission, but the availability of 5-HT may be altered in defined brain targets, as is the case for other spontaneous cerebellar mutants, in particular for the 'Lurcher' mutant mouse, a model of human olivopontocerebellar atrophy.

Animals↗
PubMed1998

Neuroleptics and dopamine transporters.

The effects of neuroleptic treatments on dopamine transporters and on dopamine receptors was investigated in the forebrain of adult rats treated for 21 days with either haloperidol, clozapine or saline. The dopamine D1 receptors, labeled with [3H]SCH23390, increased in nucleus accumbens, latero-dorsal rostral neostriatum and substantia nigra, after clozapine but not haloperidol. The dopamine D2 receptors, studied with [3H]raclopride, increased in nucleus accumbens and in dorso-lateral, ventro-medial and dorso-medial quadrants of the rostral neostriatum after either haloperidol or clozapine treatments, and also in latero-ventral rostral neostriatum but only after haloperidol. Haloperidol also up-regulated D2 receptors in rostral and caudal neostriatum, but clozapine produced a more uneven increase, especially in caudal neostriatum. In contrast, the densities of dopamine uptake sites, or transporters, labeled with [125I]RTI-121, remained unchanged after both neuroleptic treatments. The observation that dopamine transporters are resistant to treatments that modify D1 and D2 receptors indicates that these uptake sites can probably be ruled out as the target of neuroleptic drugs, and that dopamine receptor up-regulations can indeed occur independently of the densities of nerve endings at the terminal fields of innervation.

Animals↗
PubMed1998

Serotonin neural adaptations to ontogenetic loss of dopamine neurons in rat brain.

In rat, the neonatal destruction of nigrostriatal dopamine (DA) neurons by intracerebral administration of 6-hydroxydopamine entails dramatic changes in serotonin (5-hydroxytryptamine, 5-HT) as well as DA function. Most striking is the 5-HT hyperinnervation of the adult neostriatum, associated with increases in density of various 5-HT receptor subtypes and enhanced neuronal responsiveness to the iontophoretic application of 5-HT and its 5-HT(1B/2C) and 5-HT(2A/2C) receptor agonists, m-chlorophenylpiperazine and iododimethoxyphenylaminopropane. The topographical distribution of these changes is consistent with up-regulation and/or increased production and transport of 5-HT1B and 5-HT2A receptors by the neostriatal projection neurons, as confirmed for the 5-HT2A receptor in a recent in situ hybridization study. It is interesting that this study has also shown that increases in both 5-HT2A binding and mRNA level were abolished by chronic pretreatment with the DA agonists, apomorphine and SKF 38393, suggesting a regulatory influence of DA in the expression of this 5-HT receptor. D1 receptor binding is known to be slightly reduced in the rostral neostriatum of these rats, a down-regulation apparently imputable to a reduced rate of synthesis of the receptor. In contrast, D2 receptor binding is increased throughout the DA-denervated and 5-HT-hyperinnervated neostriatum, perhaps due to some posttranscriptional modifications. Stereotyped and motor behaviors induced by systemic treatment with D1 and D2 agonists are markedly enhanced in these rats (behavioral supersensitivity), although priming is commonly required to unmask a latent D1 supersensitivity. In the case of oral activity, however, overt behavioral supersensitivity is induced by D1 as well as D2 agonists. Moreover, there is overt supersensitivity of oral activity in response to the 5-HT receptor agonist m-chlorophenylpiperazine, which is presumably imputable to 5-HT2C receptors and may be demonstrated even in the absence of supersensitivity to D1 receptor agonist. 5-HT adaptations, therefore, seem to play a role not only in the abnormal spontaneous behavior, but also in the behavioral supersensitivity to 5-HT as well as DA receptor agonists in these rats.

Adaptation, Physiological↗
PubMed1997

Effects of a chronic lithium treatment on central dopamine neurotransporters.

The objectives of this study were to characterize the effects of a chronic lithium (Li+) treatment on dopamine (DA) uptake sites, as well as on the levels of mRNA encoding for these transporters, and to determine the eventual reversibility of the treatment. Quantitative autoradiography was carried out on sections from rat brain using 3beta-(4-[125I]iodophenyl)tropane-2beta-carboxylic acid isopropyl ester ([125I]RT1-121) to label DA transporters, and mRNA levels were measured by in situ hybridization. Following chronic Li+ treatment (28 days), the labelling to DA transporters increased (60-90%) in all sections of the rostral and caudal neostriatum, whereas no alteration was observed in the other regions studied, namely the substantia nigra, the ventral tegmental area, and the dorsal raphe nucleus. These effects were reversed completely following a withdrawal period of 2 days without Li+. Also, there were no modifications in the labelling of DA transporters after only 2 days of Li+ treatment. In addition, we measured the levels of mRNA encoding for DA transporters in the substantia nigra and the ventral tegmental area; however, no alterations were observed following a chronic Li+ treatment, and thus the hypothesis of an increased synthesis is not supported. This could mean that the Li+ treatment modified the affinity of DA transporters for the radioligand, possibly a consequence of conformational changes induced by the disruption of the nerve terminal membrane environment; however, a modification in the number of transporters could not be ruled out. The results of this study further support the hypothesis of the implication of central dopaminergic transmission in the pathology and treatment of affective disorders.

Animals↗
PubMed1997

Regulation of central serotonin transporters by chronic lithium: an autoradiographic study.

The objectives of this study were to further characterize the effects of a chronic lithium (Li+) treatment on serotonin (5-HT) uptake sites, and to determine the eventual reversibility of the observed effects. Quantitative autoradiography experiments were carried out on sections from rat brain, using [3H]citalopram to label selectively the 5-HT transporters or uptake sites. In these experiments, we were able to saturate the 5-HT transporters using an isotopic dilution of the radioligand. The lowest densities of [3H]citalopram binding were measured in all cortical regions studied, with the highest cortical labelling in the anterior cingulate cortex. The rostral neostriatum presented a moderate density of labelling, with slightly higher levels in its ventral portion. Relatively high densities were measured in the globus pallidus, hippocampus, and hypothalamus. Finally, the highest densities were found in the brain stem. Indeed, the dorsal raphe nuclei as well as the substantia nigra were characterized by very high amounts of [3H]citalopram binding. The chronic administration of Li+ increased the density of 5-HT uptake sites in cortical regions, and significant differences were observed in the frontal, temporal, and entorhinal-piriform cortices, with an elevation, albeit not significant, in the anterior cingulate region. A significant increase was also observed in the lateral hypothalamus. Since the 5-HT uptake sites were studied with saturating concentrations of citalopram, we can propose that this increase in binding densities can be attributed to an increase in the number of 5-HT transporters. Interestingly, the only modifications observed were located in regions containing nerve terminals of 5-HT neurons, while regions with cell bodies remained unaffected. Moreover, these effects were completely reversed following a recovery of 48 h without Li . Also, there were no modifications in the density of 5-HT uptake sites after only 2 days of Li+. These results, suggesting an anatomically heterogenous increase in 5-HT uptake in chronically treated rats, are in accord with clinical observations and previous reports with homogenate binding assays. Finally, the conclusions from this study further support the importance of central 5-HT synaptic transmission in the pathophysiology and treatment of human affective disorders.

Animals↗