The CB1 cannabinoid receptors have been found in the rodent suprachiasmatic nucleus, and their activation suppresses the light-induced phase shift in locomotor rhythmicity of mice and hamsters. Here, we show that the CB1 receptor agonist CP55940 significantly attenuates the light-induced phase delay in rats as well. Furthermore, it blocks the light induction of c-Fos and light-induced downregulation of pERK1/2 in the SCN, and the CB1 antagonist AM251 prevents the photic induction of pERK1/2 and reduces pGSK3β after photic stimulation. Our data suggest that the modulation of the cannabinoid receptor activity may affect the photic entrainment via the setting of the SCN sensitivity to light.
- Klíčová slova
- Cannabinoid, Glycogen synthase kinase-3beta, Photic entrainment, Suprachiasmatic nucleus, c-Fos, p42/44 mitogen-activated protein kinase,
- MeSH
- agonisté kanabinoidních receptorů farmakologie MeSH
- antagonisté kanabinoidních receptorů farmakologie MeSH
- cyklohexanoly farmakologie MeSH
- nucleus suprachiasmaticus účinky léků fyziologie účinky záření MeSH
- piperidiny farmakologie MeSH
- pohybová aktivita účinky léků účinky záření MeSH
- potkani Wistar MeSH
- pyrazoly farmakologie MeSH
- světlo MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol MeSH Prohlížeč
- agonisté kanabinoidních receptorů MeSH
- AM 251 MeSH Prohlížeč
- antagonisté kanabinoidních receptorů MeSH
- cyklohexanoly MeSH
- piperidiny MeSH
- pyrazoly MeSH
OBJECTIVE: Monoamine oxidase (MAO), the enzyme responsible for metabolism of monoamine neurotransmitters, has an important role in the brain development and function, and MAO inhibitors have a range of potential therapeutic uses. We investigated systematically in vitro effects of pharmacologically different antidepressants and mood stabilizers on MAO activity. METHODS: Effects of drugs on the activity of MAO were measured in crude mitochondrial fraction isolated from cortex of pig brain, when radiolabeled serotonin (for MAO-A) or phenylethylamine (for MAO-B) was used as substrate. The several antidepressants and mood stabilizers were compared with effects of well known MAO inhibitors such as moclobemide, iproniazid, pargyline, and clorgyline. RESULTS: In general, the effect of tested drugs was found to be inhibitory. The half maximal inhibitory concentration, parameters of enzyme kinetic, and mechanism of inhibition were determined. MAO-A was inhibited by the following drugs: pargyline > clorgyline > iproniazid > fluoxetine > desipramine > amitriptyline > imipramine > citalopram > venlafaxine > reboxetine > olanzapine > mirtazapine > tianeptine > moclobemide, cocaine >> lithium, valproate. MAO-B was inhibited by the following drugs: pargyline > clorgyline > iproniazid > fluoxetine > venlafaxine > amitriptyline > olanzapine > citalopram > desipramine > reboxetine > imipramine > tianeptine > mirtazapine, cocaine >> moclobemide, lithium, valproate. The mechanism of inhibition of MAOs by several antidepressants was found various. CONCLUSIONS: It was concluded that MAO activity is acutely affected by pharmacologically different antidepressants at relatively high drug concentrations; this effect is inhibitory. There are differences both in inhibitory potency and in mechanism of inhibition between both several drugs and the two MAO isoforms. While MAO inhibition is not primary biochemical effect related to their therapeutic action, it can be supposed that decrease of MAO activity may be concerned in some effects of these drugs on serotonergic, noradrenergic, and dopaminergic neurotransmission.
- MeSH
- afekt účinky léků MeSH
- amitriptylin farmakologie MeSH
- antidepresiva farmakologie MeSH
- antimanika farmakologie MeSH
- benzodiazepiny farmakologie MeSH
- citalopram farmakologie MeSH
- cyklohexanoly farmakologie MeSH
- desipramin farmakologie MeSH
- fluoxetin farmakologie MeSH
- imipramin farmakologie MeSH
- inhibitory MAO farmakologie MeSH
- iproniazid farmakologie MeSH
- klorgylin farmakologie MeSH
- kokain farmakologie MeSH
- kyselina valproová farmakologie MeSH
- lithium farmakologie MeSH
- mianserin analogy a deriváty farmakologie MeSH
- mirtazapin MeSH
- mitochondrie účinky léků enzymologie MeSH
- moklobemid farmakologie MeSH
- monoaminoxidasa účinky léků metabolismus MeSH
- morfoliny farmakologie MeSH
- mozková kůra cytologie MeSH
- olanzapin MeSH
- pargylin farmakologie MeSH
- prasata MeSH
- reboxetin MeSH
- techniky in vitro MeSH
- thiazepiny farmakologie MeSH
- venlafaxin hydrochlorid MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- amitriptylin MeSH
- antidepresiva MeSH
- antimanika MeSH
- benzodiazepiny MeSH
- citalopram MeSH
- cyklohexanoly MeSH
- desipramin MeSH
- fluoxetin MeSH
- imipramin MeSH
- inhibitory MAO MeSH
- iproniazid MeSH
- klorgylin MeSH
- kokain MeSH
- kyselina valproová MeSH
- lithium MeSH
- mianserin MeSH
- mirtazapin MeSH
- moklobemid MeSH
- monoaminoxidasa MeSH
- morfoliny MeSH
- olanzapin MeSH
- pargylin MeSH
- reboxetin MeSH
- thiazepiny MeSH
- tianeptine MeSH Prohlížeč
- venlafaxin hydrochlorid MeSH
- MeSH
- antibakteriální látky antagonisté a inhibitory MeSH
- Bacteria účinky léků MeSH
- cyklohexanoly analogy a deriváty farmakologie MeSH
- cyklohexylaminy analogy a deriváty farmakologie MeSH
- deoxycukry farmakologie MeSH
- dextrany farmakologie MeSH
- mikrobiální testy citlivosti MeSH
- sírany farmakologie MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antibakteriální látky MeSH
- cyklohexanoly MeSH
- cyklohexylaminy MeSH
- deoxycukry MeSH
- dextrany MeSH
- sírany MeSH
