Inhibition by 5-HT7 receptor stimulation of GABAA receptor-activated current in cultured rat suprachiasmatic neurones

Abstract

1. Whole-cell voltage-clamp recordings were made from postnatal rat suprachiasmatic (SCN) neurones to investigate possible modulation by 5-hydroxytryptamine (5-HT) of gamma-aminobutyric acid (GABA)-activated current (IGABA). 2. 5-HT reversibly inhibited IGABA in a concentration-dependent manner (10(-10) to 10(-6) M). (+/-)-8-Hydroxy-2-N,N-dipropylaminotetralin (8-OH-DPAT, 10(-10) to 10(-5) M) and 5-carboxamidotryptamine (10(-6) M) also inhibited IGABA, whereas 1-(2,5-dimethyl-4-iodophenyl)-2-aminopropane (DOI, 10(-6) M) had no significant effect. 3. The effect of 8-OH-DPAT (10(-7) M) was blocked by ritanserin (10(-7) M), but not by pindolol (10(-7) M). The effect of 5-HT was also suppressed by ritanserin, but not by pindolol, ketanserin (10(-7) M) or ICS 205-930 (10(-6) M). 4. 8-Bromo-cAMP (10(-3) M) or forskolin (5 x 10(-5) M) suppressed IGABA. The effects of forskolin and 5-HT were not additive. Furthermore, the effect of 5-HT (10(-7) M) was significantly reduced by N-[2-(methylamino)ethyl]-5-isoquinoline sulphonamide (H-8, 10(-6) M). 5. It is concluded that 5-HT inhibits IGABA in the SCN neurones, which involves the activation of 5-HT7 receptors and cAMP-coupled systems.