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Interaction between tricyclic and nontricyclic 5-hydroxytryptamine uptake inhibitors and the presynaptic 5-hydroxytryptamine inhibitory autoreceptors in the rat hypothalamus.
- Source :
-
The Journal of pharmacology and experimental therapeutics [J Pharmacol Exp Ther] 1985 Oct; Vol. 235 (1), pp. 200-11. - Publication Year :
- 1985
-
Abstract
- 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.
- Subjects :
- 5-Methoxytryptamine pharmacology
Amitriptyline pharmacology
Animals
Citalopram
Electric Stimulation
Fenclonine pharmacology
Hypothalamus drug effects
Hypothalamus metabolism
Imipramine pharmacology
Lysergic Acid Diethylamide pharmacology
Male
Methiothepin pharmacology
Neurotransmitter Agents metabolism
Pargyline pharmacology
Paroxetine
Rats
Rats, Inbred Strains
Antidepressive Agents, Tricyclic pharmacology
Piperidines pharmacology
Propylamines pharmacology
Receptors, Serotonin metabolism
Serotonin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3565
- Volume :
- 235
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The Journal of pharmacology and experimental therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 2864432