The effects of 5-HT uptake- and MAO-inhibitors on l-5-HTP-induced excitation in rats

Abstract

The behavioural syndrome caused by L-5-HTP in rats was used for the study of effects of selective 5-HT uptake inhibitors and inhibitors of MAO on central 5-HT receptors. A good correlation was found between the relative potencies of drugs in inhibiting the 5-HT uptake in the rat brain and in intensifying L-5-HTP-induced behavioural stimulation. The potentiation of the L-5-HTP syndrome by the MAO inhibitors correlated with the inhibition of the A- but not of the B-form of the brain monoamine oxidase. In rats treated with the maximally inhibiting dose of a 5-HT uptake inhibitor, MAO inhibitors were still able to increase the intensity of the L-5-HTP syndrome, while the combination of maximal doses of two 5-HT uptake inhibitors did not produce a more intense syndrome than that produced by one 5-HT uptake inhibitor alone. The L-5-HTP-induced behavioural syndrome in rats seems to afford an experimental model allowing the quantification and characterization of the interaction of drugs with serotonin metabolism in the brain.

Pharmacological Blockade of 5-HT7 Receptors as a Putative Fast Acting Antidepressant Strategy

“…This effect was, however, smaller in amplitude than that produced by fluoxetine, suggesting that the increase of cerebral 5-HT level induced by fluoxetine and 5-HTP activates a larger number of 5-HT receptors to induce HTR. Similarly, several studies have previously shown that ADs including SSRIs (citalopram, escitalopram, and fluoxetine) and monoamine oxidase inhibitors (tranylcypromine, pargyline) potentiate the 5-HTP-induced behavioral syndrome (Ortmann et al, 1980;Shimomura et al, 1981;Hyttel et al, 1992;Stórustovu et al, 2004;Sánchez and Kreilgaard, 2004). Notably, the 5-HT 7 receptor antagonist SB-269970 did not modify the 5-HTP-induced HTR but prevented both the AS19-and fluoxetine-stimulating effects.…”

The 5‐HT syndrome in rats as tool for the screening of psychoactive drugs

“…The behavioral syndrome induced by L-5-HTP in rats has been used in our laboratory to study the interaction of drugs with the central 5-HT system of rats [Ortmann et al, 1980[Ortmann et al, , 1981a. The method employed for the evaluation of the intensity of behavioral stimulation has been described in detail [Ortmann et al, 19801.…”

Effects of 8‐OHDPAT and 5‐HT1A antagonists WAY100135 and WAY100635, on guinea‐pig behaviour and dorsal raphe 5‐HT neurone firing

“…Presynaptic 5-HT depletion does not affect the 8-OHDPAT-induced syndrome in either rats or mice (Dourish et al, 1985;Yamada et al, 1988) indicating that the elements of the 5-HT syndrome are mediated via postsynaptic An increase in 5-HT synthesis and hence 5-HT levels (Hess & Doepfner, 1961;Grahame-Smith 1971a;Ortmann et al, 1980) also elicits the syndrome, as do the direct agonists 5-methoxy-N,N-dimethyltryptamine (Grahame-Smith 1971b;Green et al, 1981), 5-methoxytryptamine (Green et al, 1976), (+ )-lysergic acid diethylamide (LSD) (Trulson & Jacobs, 1976a) and quipazine (Green et al, 1976;. Furthermore 5-HT releasers such as fenfluramine and p-chloroamphetamine (Trulson & Jacobs, 1976b;Deakin & Green, 1978) also cause elements of the 5-HT syndrome.…”