Effect of γ-mangostin through the inhibition of 5-hydroxytryptamine_2A receptors in 5-fluoro-α-methyltryptamine-induced head-twitch responses of mice

Abstract

1. Intracerebronventricular (i.c.v.) injection of γ-mangostin (10–40 nmol/mouse), a major compound of the fruit hull of Garcinia mangostana Lin., like ketanserin (10, 20 nmol/mouse, i.c.v.) inhibited 5-fluoro-α-methyltryptamine (5-FMT) (45 mg kg⁻¹, i.p.)-induced head-twitch response in mice in the presence or absence of citalopram (a 5-hydroxytryptamine (5-HT)-uptake inhibitor).

2. Neither the 5-FMT- nor the 8-hydroxy-2-(di-n-propylamino)tetralin (5-HT_1A-agonist)-induced 5-HT syndrome (head weaving and hindlimb abduction) was affected by γ-mangostin or ketanserin.

3. The locomotor activity stimulated by 5-FMT through the activation of α₁-adrenoceptors did not alter in the presence of γ-mangostin.

4. 5-HT-induced inositol phosphates accumulation in mouse brain slices was abolished by ketanserin. γ-Mangostin caused a concentration-dependent inhibition of the inositol phosphates accumulation.

5. γ-Mangostin caused a concentration-dependent inhibition of the binding of [³H]-spiperone, a specific 5-HT_2A receptor antagonist, to mouse brain membranes.

6. Kinetic analysis of the [³H]-spiperone binding revealed that γ-mangostin increased the K_d value without affecting the B_max value, indicating the mode of the competitive nature of the inhibition by γ-mangostin.

7. These results suggest that γ-mangostin inhibits 5-FMT-induced head-twitch response in mice by blocking 5-HT_2A receptors not by blocking the release of 5-HT from the central neurone. γ-Mangostin is a promising 5-HT_2A receptor antagonist in the central nervous system.

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