Monoamine receptor sensitivity changes following chronic administration of MDL 72394, a site-directed inhibitor of monoamine oxidase

Palfreyman, Michael G.; Mir, Anis K.; Kubina, Martial; Middlemiss, Derek N.; Richards, Mary H.; Tricklebank, Mark D.; Fozard, John R.

doi:10.1016/0014-2999(86)90185-8

Cited by 23 publications

(7 citation statements)

References 62 publications

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“…The decrease in the electrically evoked 5‐HT efflux induced by the 5‐HT 1A agonist 8‐OH‐DPAT (1 μM) was significantly greater in the wild type (38%) than in the MAOA‐KO (21%) mice. These authors suggested that the autoreceptor control of amine efflux in the dorsal raphe may be blunted in mutants, which is consistent with the decrease in the number of 5‐HT 1A binding sites observed after chronic MAO inhibitor administration (Palfreyman et al,1986); this reduced control of 5‐HT efflux in the raphe probably reflects a compensatory response to the chronic elevation of 5‐HT in MAOA‐KO mice.…”

Section: Discussionsupporting

confidence: 59%

Reduced density of functional 5-HT1A receptors in the brain, medulla and spinal cord of monoamine oxidase-A knockout mouse neonates

2006

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Abnormally high brain 5-HT levels in monoamine oxidase-A knockout (MAO-A KO) mouse neonates raise the question of whether the distribution and density of the 5-HT1A receptors (5-HT1AR) expressed in the brain by postnatal day P7 are affected and, if so, whether the 5-HT1A autoreceptors in the dorsal raphe are modified in the same way as the postsynaptic 5-HT1AR present in raphe target structures. [3H]8-OH-DPAT binding and quantitative autoradiography were performed to answer these questions. Binding specificity was first confirmed in adult wild-type mice and rat brain sections. 5-HT1AR binding was then analyzed in four MAO-A mutant vs. five wild-type neonatal brains, from olfactory bulb to cervical cord. Among 12 structures expressing postsynaptic 5-HT1AR in wild-type neonates, the highest densities involved the retrosplenial cortex, entorhinal cortex, and septum (52-46 fmol/mg tissue); low densities occurred in the hippocampus and spinal cord (24 fmol/mg tissue); in addition, the raphe autoreceptor density was only 20 fmol/mg tissue. In mutants, the distribution of postsynaptic 5-HT1AR was unchanged, but an overall decrease in density occurred (-32% to -63%); the raphe autoreceptors decreased in mutants by at least -79%. Data are discussed with reference to the ectopic 5-HT uptake and accumulation reported to occur during the first 10 postnatal days in wild-type and MAO-A KO mice. As previously suggested to explain the raphe autoreceptor loss in 2-month-old MAO-A KO mice, the overall 5-HT1AR down-regulation in mutant pups probably results from extracellular 5-HT excess in both raphe and target structures. The greater the 5-HT excess, the more the functional receptor density decreases.

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Section: Discussionsupporting

confidence: 59%

Reduced density of functional 5-HT1A receptors in the brain, medulla and spinal cord of monoamine oxidase-A knockout mouse neonates

2006

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“…Subchronic treatment with imipramine (10 mg/kg, i.p., twice a day for 14 days) did not change the 5-HT1A receptor number in rat cerebral cortex (unpublished observation). Repeated treatment of rats with monoamine oxidase inhibitors was reported to downregulate 5-HT1A receptor number (Palfreyman et al, 1987). Accordingly, although it is likely that all of the drugs used to commit suicide produce respiratory depression and hypoxia, it is unlikely that these agents, which are chemically distinct from each other [benzodiazepine, barbiturates, antidepressant (doxepine), neuroleptics (thioridazine) or analgesics], produce a net upregulation of 5-HT1A receptor binding sites.…”

Section: Discussionmentioning

confidence: 98%

Serotonergic measures in suicide brain: 5-HT1A binding sites in frontal cortex of suicide victims

Matsubara

Arora

Meltzer

1991

J. Neural Transmission

142

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The density of 5-HT1A binding using 3H-8-hydroxy-2-(di-n-propyl-amino) tetralin (8-OH-DPAT) as binding ligand, was studied in human frontal cortex of suicide victims and normal controls who died due to medical disease or accidentally. There was no difference in the maximum number of binding site (Bmax) or Kd (an inverse measure of affinity) of 5-HT1A receptor binding sites between normal controls and the entire group of suicide victims. However, nonviolent suicides had significantly higher Bmax (22-25%) compared to both controls and violent suicides. A negative correlation between age and Bmax of 5-HT1A binding sites was found in male controls but not in female controls or suicide victims. This relationship was less apparent among the male controls over age 60.

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“…This result suggested that short-term exposure to an elevated synaptic concentration of NE does not desensitize a2-adrenergic heteroreceptors on S-HT terminais. However, long-term NE reuptake blockade with desipramine or long-term MAO inhibition with MDL 72394 or pargyline has not been reported to change the ability of a2-adrenergic heteroreceptors to reduce the electrically induced release of 1 3 H]S-HT in rat cortical and hippocampal slices (Schlicker et al 19R2;Palfreyman et al 1986). FinaUy, another study using rat brain synaptosomes revealed that the attenuation of K+-stimulated release of [3H]S-HT by c10nidine was diminished following a long-term treatment with the irreversible MAO inhibitor c10rgyline but not by desipramine (Ellison and Campbell 1986).…”

Section: Discussionmentioning

confidence: 99%

“…slUdies have shown thatlongtenD treattnents with monoamine oxidase inhibitors increase the release of [3H]noradrenaIine but do not change the sensitivity of the cx2-adrenergic autoreceptors in the hippocampus (Campbell and McKernan. 1986;Palfreyman et al. 1986;Blier and Bouchard.…”

Section: Discussionmentioning

confidence: 99%

The serotonergic and noradrenergic systems of the hippocampus: their interactions and the effects of antidepressant treatments

Mongeau

Blier

Montigny

1997

Brain Research Reviews

348

213

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Monoamine receptor sensitivity changes following chronic administration of MDL 72394, a site-directed inhibitor of monoamine oxidase

Cited by 23 publications

References 62 publications

Reduced density of functional 5-HT1A receptors in the brain, medulla and spinal cord of monoamine oxidase-A knockout mouse neonates

Reduced density of functional 5-HT1A receptors in the brain, medulla and spinal cord of monoamine oxidase-A knockout mouse neonates

Serotonergic measures in suicide brain: 5-HT1A binding sites in frontal cortex of suicide victims

The serotonergic and noradrenergic systems of the hippocampus: their interactions and the effects of antidepressant treatments

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