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. © 1994 The Physiological Society