Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • rat  (115)
  • 1
    ISSN: 1435-1463
    Keywords: Substituted amphetamines ; PCA (p-chloroamphetamine) ; MDMA (3,4-methylenedioxymethamphetamine) ; serotonin ; tryptophan hydroxylase ; paroxetine binding ; 5-HT transporter density ; neurotoxicity ; strain differences ; rat ; cortex
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Substituted amphetamines are known to selectively destroy serotonin (5-HT) nerve endings in distant projection fields of the dorsal raphe nuclei and the systemic administration of these drugs is widely used in investigations of the role of the central 5-HT system and of the mechanisms involved in their toxicity. Until now Sprague-Dawley rats were almost exclusively used for this purpose and the findings were thought to apply to other strains as well. We compared the long-term effects of the administration of different doses of para-chloroamphetamine (PCA) on three specific markers of the density of 5-HT presynapses, [3H]-paroxetine binding to 5-HT-transporters, tryptophan hydroxylase apoenzyme contents, and 5-HT levels in the frontal cortex of Sprague-Dawley and Wistar rats. PCA-treatment caused a dose dependent decline of all three parameters which was much more pronounced in Sprague-Dawley compared to Wistar rats. An i.p. dose of 4mg PCA/kg body weight, which caused a severe, about 90% reduction of all three parameters of 5-HT innervation in Sprague-Dawley rats was almost ineffective in Wistar rats. The dose of 8mg/kg which was required to eliminate about 80% of cortical 5-HT presynapses in Wistar rats was already lethal to Sprague-Dawley rats. The reasons of this different susceptibility of the 5-HT system in the two rat strains are unknown. Their elucidation will contribute to a better understanding of inherited differences in individual vulnerability to the neurotoxic effects of substituted amphetamines. The combined measurements of transporter density, of tryptophan hydroxylase apoenzyme contents, and of 5-HT levels is a powerful tool for the assessment of experimentally induced changes in the density of 5-HT innervation in distant projection fields of the raphe nuclei.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    ISSN: 1435-1463
    Keywords: Ventral tegmental area ; substantia nigra pars compacta ; extracellular recording ; excitatory amino acids ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Evidence suggests that the prefrontal cortex (PFC) plays an important role in the burst activity of midbrain dopaminergic (DA) neurons. In particular, electrical stimulation of the PFC elicits patterns of activity in DA neurons, closely time-locked to the stimulation, which resemble natural bursts. Given that natural bursts are produced by the activity of excitatory amino acid (EAA)-ergic afferents, if PFC-induced time-locked bursts are homologues of natural bursts, EAA antagonists should attenuate them. Hence, the NMDA (N-methy1-D-aspartate) antagonist CPP (3-((±)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid) and the AMPA (D,L-α-amino-3-hydroxy-5-methyl-4-isoxalone propionic acid)/kainate antagonist CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) were applied by iontophoresis to DA neurons exhibiting time-locked bursts during PFC stimulation. CPP produced a significant reduction in time-locked bursting. In contrast, CNQX (at currents which antagonised AMPA responses) did not. These effects of CPP and CNQX on time-locked bursting mirror the effects previously reported for these drugs on natural bursting. Since natural bursting and bursting induced by PFC stimulation are both blocked selectively by CPP, the present results increase the degree of analogy between the two burst phenomena, thereby adding extra support to the contention that the cortex is involved in producing the natural bursting in DA neurons.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    ISSN: 1435-1463
    Keywords: Anticonflict ; benzodiazepine receptor ; noradrenaline ; rat ; serotonin ; yohimbine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The α2-adrenoceptor antagonist yohimbine has in several previous studies been found to produce anticonflict effects comparable to those produced by the benzodiazepines (BDZ) in rat punished conflict models. In this and a following paper we have tried to elucidate the neurochemical mechanisms underlying these effects in a modified Vogel's drinking conflict test. Since yohimbine previously has been demonstrated to interfere both with noradrenaline (NA) and serotonin (5-HT) neurochemistry, and, in addition, shows affinity for the BDZ binding site, we have focused on the putative involvement of these neuronal systems in the yohimbine-induced anticonflict effect. The α2-adrenoceptor agonist clonidine (10 μg/kg, i.p.) completely antagonized the anticonflict effect of yohimbine (4.0 mg/kg, i.p.), whereas the α1-adrenoceptor agonist ST 587 (1.0 mg/kg, i.p.) had no effect. The anticonflict effect of yohimbine was totally abolished also following lesioning of NA neurons with 6-hydroxy-dopamine. A high dose of the mixed β1 and β2 adrenoceptor antagonist propranolol (8.0 mg/kg, i.p.) caused a partial blockade of the yohimbine-induced effect in intact animals, whereas the selective β1-adrenoceptor antagonist metoprolol (4.0 mg/kg, i.p.) had no significant effect and the α1-adrenoceptor antagonist prazosin instead potentiated the anticonflict action. The anticonflict effect of yohimbine was dose-dependently antagonized also by the 5-HT precursor L-5-hydroxytryptophan (25–100 mg/ kg, i.p.). The BDZ receptor antagonist flumazenil (10 mg/kg, p.O.), as well as Ro 15-4513 (1.0 mg/kg, p.o.), a partial inverse agonist at BDZ receptors, partly, but significantly, counteracted the yohimbine-induced anticonflict effect, whereas low doses of both the chloride channel blocker picrotoxin and the GABAA antagonist bicuculline only tended to counteract the yohimbine effect. Taken together, the results in the present behavioral paper indicate that the anticonflict effect of yohimbine involves both increased NA and decreased 5-HT activity, and that direct or indirect activation of BDZ receptors may also be involved. Neurochemical findings related to these behavioral results are presented in a following paper.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    ISSN: 1435-1463
    Keywords: Anticonflict ; GABA a /benzodiazepine receptor complex ; noradrenaline ; rat ; serotonin ; yohimbine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a companion paper the α2-adrenoceptor antagonist yohimbine was found to produce a dose-dependent anticonflict effect in a modified Vogel's conflict test. The behavioral data further indicated that noradrenergic and serotonergic neurons as well as the benzodiazepine (BDZ) receptor may be involved in the anticonflict effect of yohimbine. In the present study the effects on rat brain monoamine neurochemistry and GABA a /BDZ receptor function (36Cl−-uptake in corticohippocampal synaptoneurosomes) of a maximally anticonflict producing dose of yohimbine (4.0 mg/kg, i.p.) were studied. The levels of rat brain catecholamines and indoleamines were measured ex vivo using high performance liquid chromatography with electrochemical detection (HPLC-ED). Yohimbine decreased noradrenaline levels both in the hippocampus and the hemispheres but instead increased DOPAC levels in these brain regions as well as in the limbic forebrain. Yohimbine also markedly enhanced DOPA accumulation in the hippocampus and the hemispheres after inhibition of 1-aromatic amino acid decarboxylase by means of NSD 1015, whereas in the limbic system only a modest increase was obtained. The yohimbine-induced effects on the catecholamine synthesis rate were largely abolished in animals severely depleted of NA by means of 6-hydroxy-dopamine (6-OH-DA) pretreatment. Yohimbine decreased both the 5-HIAA/5-HT quotient (an indicator of 5-HT turnover) and 5-HTP accumulation after NSD 1015 in the hemispheres, whereas in the hippocampus and the limbic system only 5-HTP accumulation was decreased. The yohimbine-induced effect on the indoleamine synthesis rate was not influenced by 6-OH-DA pretreatment, whereas this effect and that on the catecholamine synthesis rate were both abolished by reserpine pretreatment. Neither in vivo nor in vitro administration of yohimbine significantly altered baseline or GABA-induced accumulation of36Cl− in corticohippocampal synaptoneurosomes. In conclusion, the present study provides neurochemical support for the suggestion that yohimbine may exert its anticonflict effect in a modified Vogel's conflict test by increasing and decreasing NA and 5-HT neurotransmission, respectively, whereas no evidence was obtained for a direct interaction of yohimbine with GABA a /BDZ receptor function.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    ISSN: 1435-1463
    Keywords: 5-HT1a ; 5-HT1b ; 5-HT3 receptors ; rat ; spinal cord ; rhizotomy ; DSP-4, 5,7-DHT ; autoradiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Autoradiographic studies were performed in combination with dorsal rhizotomy or selective lesion of descending serotonergic or noradrenergic systems in an attempt to identify the neuronal cell types endowed with the serotonin 5-HT1a , 5-HT1b and 5-HT3 receptors in the rat spinal cord. Unilateral sectioning of seven dorsal roots (C4–T2) at the cervical level produced a marked decrease (∼−75%, 10 days after the surgery) in the binding of [125I]iodozacopride to 5-HT3 receptors in the superficial layers of the ipsilateral dorsal horn, further confirming the preferential location of these receptors on primary afferent fibres. In addition, a significant decrease (∼20%) in the binding of [3H]8-OH-DPAT to 5-HT1A receptors and of [125I]GTI to 5-HT1B receptors was also observed in the same spinal area in rhizotomized rats, suggesting that a small proportion of these receptors are also located on primary afferent fibres. The labelling of 5-HT1B receptors was significantly decreased (−12%) in the dorsal horn at the cervical (but not the lumbar) level, and that of 5-HT3 receptors was unchanged in the whole spinal cord in rats whose descending serotonergic projections had been destroyed by 5,7-dihydroxytryptamine. Conversely, the labelling of 5-HT1A receptors was significantly increased in the cervical (+13%) and lumbar (+42%) dorsal horn in 5,7-dihydroxytryptamine-lesioned rats. Similarly, [3H]8-OH-DPAT binding to 5-HT1A receptors significantly increased (+26%) in the lumbar (but not the cervical) dorsal horn in rats whose noradrenergic systems had been lesioned by DSP-4. The labelling of 5-HT1B receptors was also increased (+31% at the cervical level; +17% at the lumbar level), whereas that of 5-HT3 receptors remained unchanged in these animals. These data indicate that complex adaptive changes in the expression of 5-HT1A and 5-HT1B receptors occurred in the rat spinal cord following the lesion of descending monoaminergic systems.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    ISSN: 1435-1463
    Keywords: Phencyclidine (PCP) ; neural visinin-like Ca2+-binding protein (NVP) ; gene expression ; rat ; brain ; schizophrenia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Phencyclidine (PCP) induces a psychotomimetic state that closely resembles schizophrenia, and PCP-treated animals can serve as a model for schizophrenia. The effects of PCP on the gene expression of NVP-1, a novel Ca2+-binding protein, were studied in rats. After 24 hours, the NVP-1 mRNA level in the nucleus accumbens showed a significant decrease of 42%. This result suggests that alterations in Ca2+-binding protein may be involved in the pathology of PCP-induced psychosis and, presumably, schizophrenia.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    ISSN: 1435-1463
    Keywords: D3 receptor ; conditioned place preference ; intracranial self-stimulation ; 7-OH-DPAT ; (+)-3PPP ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Compounds showing an in vitro binding preference for the dopamine D3 receptor were tested in two models designed to assess positive reinforcement in the rat: intracranial self-stimulation (ICSS) and conditioned place preference (CPP). R-(+)-7-OH-DPAT, a D3 preferring agonist, inhibited ICSS behaviour over a wide dose range. At higher doses, a facilitation of ICSS was seen. In the CPP model, 7-OH-DPAT was inactive except at the highest dose where a significant change in preference was seen. A dose of R-(+)-7-OH-DPAT, that significantly inhibited ICSS behaviour, was combined with a dose of d-amphetamine, that significantly facilitated ICSS behaviour. Surprisingly, this resulted in a significant synergistic facilitation of the amphetamine response. The putative D3 antagonist, U99194A was inactive in the ICSS model but induced significant place preference. The present results suggest that the dopamine D3 receptor, in contrast to the D2 receptor, has an inhibitory influence on reward mechanisms.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    ISSN: 1435-1463
    Keywords: [3H]S-14506 ; [3H]8-OH-DPAT ; guanine nucleotides ; N-ethyl-maleimide ; 5-HT1A receptors ; autoradiography ; in vivo labeling ; rat ; mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The tritiated derivative of the potent 5-HT1A receptor agonist S-14506 {1[2-(4-fluorobenzoylamino)ethyl]-4-(7-methoxynaphtyl)piperazine} was tested for its capacity to selectively label the serotonin 5-HT1A receptors both in vitro in the rat and the mouse brain, and in vivo in the mouse. In vitro studies showed that the pharmacological profile and the distribution of [3H]S-14506 specific binding sites (Kd=0.15 nM) in different brain regions matched perfectly those of the prototypical 5-HT1A receptor ligand [3H]8-OH-DPAT. However, in the three regions examined (hippocampus, septum, cerebral cortex), the density of [3H]S-14506 specific binding sites was significantly higher (+ 66–90%) than that found with [3H]8-OH-DPAT. Whereas the specific binding of [3H]8-OH-DPAT was markedly reduced by GTP and Gpp(NH)p and increased by Mn2+, that of [3H]S-14506 was essentially unaffected by these compounds. In addition, the alkylating agent N-ethylmaleimide was much less potent to inhibit the specific binding of [3H]S-14506 than that of [3H]8-OH-DPAT. Measurement of in vivo accumulation of tritium one hour after i.v. injection of [3H]S-14506 to mice revealed marked regional differences, with about 2.5 times more radioactivity in the hippocampus than in the cerebellum. Pretreatment with 5-HT1A receptor ligands prevented tritium accumulation in the hippocampus but not in the cerebellum. Autoradiograms from brain sections of injected mice confirmed the specific in vivo labeling of 5-HT1A receptors by [3H]S-14506, therefore suggesting further developments with derivatives of this molecule for positron emission tomography in vivo in man.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    ISSN: 1435-1463
    Keywords: Corticotropin releasing hormone ; thyroid hormone ; oxytocin ; vasopressin ; neuropeptides ; ageing ; human ; rat ; brain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In this paper we have investigated the distribution of corticotropin releasing hormone (CRH)-, vasopressin- and oxytocin-immunoreactive (IR) neurones in the paraventricular nucleus in the senile compared to the adult human brain. We found a higher number of CRH-IR neurones in senile compared to adult subjects. Vasopressin- and oxytocin-IR neurones were instead more weakly stained in the former compared to latter. These results support a hypothalamic involvement in promoting the higher activity of the hypothalamus-pituitary-adrenal axis and, thus, higher glucocorticoid plasma levels which have been described in the elderly.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
    ISSN: 1435-1463
    Keywords: 5-HT1A ; dopamine ; nucleus accumbens ; striatum ; rat ; microdialysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In this study we employed in vivo microdialysis to examine the effects of the selective 5-HT1A receptor antagonist (S)-5-fluoro-8-hydroxy-2-(dipropylamino)tetralin [(S)-UH-301] on extracellular concentrations of dopamine (DA) and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the nucleus accumbens (NAC) and dorsal striatum of awake freely moving rats. Systemic administration of (S)-UH-301 (1.25, 2.5, 5.0mg/kg s.c.) dose-dependently decreased extracellular concentrations of DA, DOPAC and HVA in the NAC. (S)-UH-301 (2.5mg/kg s.c.) also decreased DA, but not DOPAC and HVA, concentrations in the striatum. Infusion of low concentrations (1, 10 μM) of (S)-UH-301 into either the NAC or the striatum did not affect DA levels, while only the highest concentration (1,000 μM) significantly decreased DA levels in both areas. Similarly, infusion of the selective 5-HT1A receptor agonist (R)-8-hydroxy-2-(di-n-propylamino)tetralin [(R)-S-OH-DPAT] only in high concentrations (100, 1,000 μM) decreased DA levels in both regions. These data suggest that (S)-UH-301 decreases DA release both in the NAC and the striatum probably indirectly via its purported DA-D2/D3 receptor agonistic properties. However, the observed inhibitory effect of (S)-UH-301 on DA release in the studied brain regions may also be explained, at least partly, by a serotonergic influence on the DA systems, acting at 5-HT1A receptor sites located elsewhere in the brain.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...