In slices of the rat hypothalamus prelabeled with [3H]-5-hydroxytryptamine [( 3H]-5-HT), exposure to lysergic acid diethylamide or 5-methoxytryptamine decreased, in a concentration-dependent manner, the release of 3H-transmitter elicited by electrical stimulation. These inhibitory effects were antagonized by the 5-HT receptor antagonist methiothepin (1 microM). Exposure to methiothepin on its own increased in a concentration-dependent manner the electrically evoked overflow of [3H]-5-HT. Exposure to tricyclic antidepressants, like imipramine and amitriptyline, and to nontricyclic 5-HT uptake inhibitors, like paroxetine and citalopram, did not modify by themselves the electrically evoked overflow of [3H]-5-HT. Yet, the four inhibitors of neuronal uptake of 5-HT, antagonized the inhibition by lysergic acid diethylamide or 5-methoxytryptamine of the electrically induced release of [3H]-5-HT. After depletion of endogenous stores of 5-HT by pretreatment with para-chlorophenylalanine (300 mg/kg i.p.), the inhibitors of 5-HT uptake increased the electrically evoked release of [3H]-5-HT in a concentration-dependent manner. Their order of potency to enhance 5-HT overflow after pretreatment with parachlorophenylalanine paralleled their potency at inhibiting neuronal uptake of 5-HT (paroxetine = citalopram greater than imipramine greater than amitriptyline). In para-chlorophenylalanine-treated rat hypothalamic slices, these inhibitors of 5-HT uptake antagonized the inhibition by 5-HT autoreceptor agonists of the electrically evoked release of [3H]-5-HT to a similar extent than was observed in control rats. It is concluded that inhibition of 5-HT uptake reduces the effectiveness of 5-HT autoreceptor agonists to inhibit the electrically evoked release of [3H]-5-HT, irrespective of the chemical structure of the uptake inhibitor or of the levels of endogenous 5-HT achieved in the synaptic gap.

Autoreceptor

Tricyclic

Citalopram

10.1016/s0022-3565(25)23832-0

Cite

Citations (73)

Does 5-carboxamidotryptamine-induced turning in guinea-pigs involve 5-HT1D autoreceptors?

European Journal of Pharmacology (1993)

Chantal Moret Mike Briley

Autoreceptor

Microdialysis

10.1016/0014-2999(93)90578-6

Cite

Citations (5)

Sensitivity of the response of 5-HT autoreceptors to drugs modifying synaptic availability of 5-HT

Neuropharmacology (1988)

Chantal Moret

Pargyline

Autoreceptor

10.1016/0028-3908(88)90199-2

Cite

Citations (26)

Effect of milnacdpran and desipramine on noradrenergic α2-autoreceptor sensitivity

Progress in Neuro-Psychopharmacology and Biological Psychiatry (1994)

Chantal Moret Mike Briley

Desipramine

Autoreceptor

Guanabenz

Milnacipran

10.1016/0278-5846(94)90131-7

Cite

Citations (17)

The role and therapeutic potential of 5-HT-moduline in psychiatry

Seminars in Clinical Neuropsychiatry (2003)

Chantal Moret Brigitt Grimaldi O. Massot Gille Fillion

Autoreceptor

10.1053/scnp.2003.50013

Cite

Citations (6)

Antagonism by (+)-amphetamine of the inhibition of [3H]-noradrenaline overflow obtained by alpha-adrenoceptor agonists or bretylium in the perfused cat spleen [proceedings].

PubMed (1979)

Margarita L. Dubocovich S Z Langer Chantal Moret

Alpha (finance)

Bretylium

Source

Cite

Citations (3)

Depression: emerging research and treatment approaches. 16-17 January 2003, Paris, France.

PubMed (2003)

Chantal Moret

In contrast to the more conventional meeting structure of describing the progress from molecule to man, this meeting began by illustrating the breadth of the problem of unipolar depression. Several speakers presented data indicating that unipolar depression is now the leading cause of disability-adjusted life years(DALY) in the world. Following several presentations regarding the recent advances in understanding the pathology of depression, the progress of antidepressant therapy over the last half-century was reviewed. The difficulties encountered in demonstrating the antidepressant activity of new compounds was analyzed, as was the way in which the signal-to-noise ratio might be improved in clinical trials. New antidepressant drugs, which are expected to enter the market in the near future, were represented by the pentapeptide nemifitide (Innapharma Inc) and the 5-HT 1B, receptor antagonist AR-A2 (AstraZeneca plc). The more distant future was envisaged by discussion of the problems and promises of genomic techniques in the discovery of new drug targets.

Depression

Source

Cite

Citations (2)

High-Affinity [ ³ H]Imipramine Binding in Rat Hypothalamus: Association with Uptake of Serotonin But Not of Norepinephrine

Science (1980)

S.Z. Langer Chantal Moret Rita Raisman M. L. Dubocovich Mike Briley

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.

10.1126/science.7444441

Cite

Citations (378)

5-HT1B/D receptors in anxiety

Birkhäuser Basel eBooks (2000)

Chantal Moret

The last 30 years have seen the virtual monopoly of the anxiolytic market by benzodiazepines and more recently by the compounds which constitute the first part of this book. Among other neurotransmitters potentially involved in anxiety, serotonin (5-hydroxytryptamine, 5-HT) of course has a very prominent place. The neuropharmacology of 5-HT has been fundamentally revised in recent years with the discovery of multiple serotonin receptor subtypes [1].

Neuropharmacology

10.1007/978-3-0348-8470-9_8

Cite

Citations (0)