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Biomedical subjects

C Moret

Publications and source records attributed to C Moret.

66 records · Page 4Linked to original sources
PubMed1984

Evidence that exogenous but not endogenous norepinephrine activates the presynaptic alpha-2 adrenoceptors on serotonergic nerve endings in the rat hypothalamus.

In superfused rat hypothalamic slices, clonidine, norepinephrine (NE) and 6-fluoronorepinephrine reduced the electrically evoked release of recently taken up [3H]-5-hydroxytryptamine (5-HT). The inhibitory action of these drugs involves the activation of presynaptic alpha-2 adrenoceptors and it was antagonized by the alpha adrenoceptor antagonists phentolamine or RX 781094. In contrast to the facilitating effect of alpha-2 adrenoceptor antagonists on the electrically evoked [3H]NE overflow in rabbit hypothalamic slices, neither phentolamine nor RX 781094 modified the stimulation-evoked release of [3H]-5-HT at concentrations which completely antagonized the inhibitory action of NE, 6-fluoronorepinephrine and clonidine on 5-HT neurotransmission. In the presence of cocaine, which inhibits the neuronal uptake of NE and increases the concentration of this neurotransmitter in the synaptic gap, alpha-2 adrenoceptor antagonists were still unable to modify the electrically evoked release of [3H]-5-HT. It is concluded that presynaptic alpha-2 adrenoceptors present on serotonergic nerve endings in the hypothalamus are not activated by endogenous NE and do not seem to play a physiological role in the regulation of serotonergic neurotransmission. However, presynaptic inhibitory alpha-2 adrenoceptors can be acted upon by exogenous agonists to inhibit 5-HT release. On the other hand, the presynaptic alpha-2 adrenoceptors on noradrenergic nerve terminals in the rabbit and rat hypothalamus are acted upon by released NE because the alpha-2 adrenoceptor antagonists by themselves increase the electrically evoked release of [3H]NE.

Animals↗
PubMed1982

Citalopram antagonizes the stimulation by lysergic acid diethylamide of presynaptic inhibitory serotonin autoreceptors in the rat hypothalamus.

Slices of rat hypothalamus prelabeled with [3H]-5-hydroxytryptamine ([3H]-5-HT) were superfused and the release of the labeled transmitter was elicited either by electrical stimulation or by fenfluramine. Whereas the electrically stimulated release of [3H]-5-HT was completely abolished by removing calcium from the superfusion medium, the fenfluramine-induced release of [3H]-5-HT was calcium-independent. Methiothepin increased, in a concentration-dependent manner, the [3H]-5-HT release induced by electrical stimulation but had no effect on that elicited by fenfluramine. The 3H-transmitter release elicited by electrical stimulation was inhibited by lysergic acid diethylamide (LSD) in a concentration-dependent manner, but the release induced by fenfluramine was not modified by LSD. The reduction by LSD of [3H]-5-HT overflow elicited by electrical stimulation was antagonized by methiothepin, but unaffected by phentolamine or by sulpiride. Low concentrations (10-1000 nM) of citalopram, a 5-HT uptake inhibitor, antagonized the inhibition by LSD of electrically evoked release of [3H]-5-HT. These concentrations of citalopram did not modify by themselves the overflow of [3H]-5-HT elicited by electrical stimulation. It is concluded that the modulation of [3H]-5-HT release by presynaptic serotonin autoreceptors is not operational when the neurotransmitter is released through a calcium-independent mechanism. The potent presynaptic inhibition by LSD of serotonergic neurotransmission may contribute to the central actions of this drug. The interaction between citalopram and LSD at the level of [3H]-5-HT release does not seem to involve a competitive interaction at the same receptor site. The possibility that neuronal uptake of 5-HT and the presynaptic 5-HT autoreceptor may be linked in a functional manner cannot be excluded.

Animals↗
PubMed1980

High-affinity [3H]imipramine binding in rat hypothalamus: association with uptake of serotonin but not of norepinephrine.

Inhibition of the binding of [3H]imipramine and inhibition of the uptake of [3H]serotonin and [3H]norepinephrine by a series of antidepressants and other drugs were studied in the rat hypothalamus. No correlation was found between the potencies of these drugs for the inhibition of [3H]imipramine binding and the inhibition of [3H]norepinephrine uptake. There was, however, a highly significant correlation between the potencies of these drugs for the inhibition of [3H]serotonin uptake. These results suggest that high-affinity [3H]imipramine binding might be associated with the mechanism of serotonin uptake in the brain.

Animals↗
PubMedDate not supplied

Carnitine acetyltransferase activity is not changed with age in rat brain and human platelets.

Carnitine acetyltransferase activity was studied in different brain regions of the rat and in human platelets. The values of Km for carnitine and for acetyl-CoenzymeA (acetyl-CoA) were similar in cortex, hippocampus and striatum of the rat and in human platelets, suggesting that carnitine acetyltransferase might be a useful peripheral marker of its central activity. The activity of this enzyme was similar in the cortex and hippocampus of young and old rats. Furthermore, the determination of carnitine acetyltransferase activity in platelets from healthy volunteers showed no significant difference with age.

Acetyltransferases↗
PubMedDate not supplied

5-HT autoreceptors in the regulation of 5-HT release from guinea pig raphe nucleus and hypothalamus.

5-HT autoreceptors involved in the regulation of 5-HT release in the guinea pig dorsal raphe nucleus have been studied in comparison with those in the hypothalamus. In vitro release was measured in slices of raphe and hypothalamus prelabelled with [3H]5-HT, superfused with Krebs solution and depolarized electrically. The non-selective 5-HT receptor agonist, 5-carboxamidotryptamine (5-CT) (0.1-10 nM for raphe: 1-100 nM for hypothalamus) and antagonist, methiothepin (10-1000nM), decreased and increased, respectively, the release of [3H]5-HT evoked by electrical stimulation in either of these regions when given alone. The selective 5-HT1B/D receptor antagonist, GR127935 (100-1000 nM), and the 5-HT1D receptor antagonist, ketanserin (300-1000 nM), had no significant effect on this release in either of these regions. Methiothepin and GR127935 (100-1000 nM) shifted to the right the concentration-effect curve of 5-CT in both the raphe and the hypothalamus. At 300 nM, ketanserin shifted to the right the concentration-effect curve of 5-CT in the raphe but did not modify the 5-CT curve in the hypothalamus. In microdialysis experiments ketanserin, applied locally at 10 microM, increased the extracellular levels of 5-HT in the dorsal raphe nucleus of the freely moving guinea pig, whereas 5-HT levels were unchanged in the hypothalamus. Ketanserin at 1 microM did not affect the decrease in 5-HT output induced by the selective 5-HT1B/D receptor agonist, naratriptan (used at 10 microM in raphe and 0.1 microM in hypothalamus), in the raphe or the hypothalamus. In the raphe, WAY100635, a 5-HT1A receptor antagonist, at 1 microM, did not prevent naratriptan (10 microM) from reducing the extracellular levels of 5-HT. These results suggest that, in the conditions used in this study, the release of 5-HT in the dorsal raphe nucleus is possibly modulated in part by 5-HT1B receptors but essentially the control is through 5-HT receptors whose subtype is still to be determined. In the hypothalamus, however, it is clear that only 5-HT1B receptors are involved in the modulation of 5-HT neurotransmission.

Animals↗
PubMedDate not supplied

[Monoaminergic receptors and hypotheses of the mechanisms of action of 2nd generation antidepressive agents].

The inhibition of the serotonin and/or noradrenalin reuptake is often given as the mechanism of action of antidepressants. This may be true but it's certainly wrong! The diversity of chemical structure and pharmacological profiles of second generation antidepressants shows that the biochemical property that is the most often found is the inhibition of the uptake of 5-HT and/or NA. The difference of the kinetics between the inhibition of the monoamine reuptake and the antidepressant effect is only one of the reasons to believe that the real mechanism of their antidepressant action is elsewhere. The different hypotheses that have been proposed will be examined.

Animals↗