Modulation by 5-hydroxytryptamine of the somatostatin receptor-effector system and somatostatin levels in rat brain.

Abstract

The role of 5-hydroxytryptamine (5-HT) in the acute regulation of the rat brain somatostatin (SS) receptor-effector system and somatostatin-like immunoreactivity (SSLI) content was examined. 5-HT administered i.c.v. in a volume of 10 microliters at a dose of 0.5 microgram (pH 3.4) increased the SSLI concentration at 60 min in the Wistar rat frontoparietal cortex and hippocampus (60%, P < 0.05; 72%, P < 0.01; respectively). These changes were associated with a significant increase in the total number of specific SS receptors in the frontoparietal cortex (24%, P < 0.05) and hippocampus (20%, P < 0.05), without changes in the affinity constant as compared with the control group. No significant differences were seen in the basal and forskolin (FK)-stimulated adenylate cyclase (AC) activities in both brain areas of 5-HT-treated rats when compared to the control group. The capacity of SS to inhibit the FK-stimulated AC activity in the frontoparietal cortex and hippocampus of 5-HT-treated rats was lower than in the control groups. The ability of the stable GTP analogue 5'-guanylylimidodiphosphate (Gpp(NH)p) to inhibit FK-stimulated AC activity in frontoparietal cortical and hippocampal membranes was markedly decreased in 5-HT-treated rats. To determine if the above-mentioned changes were related to the 5-HT activation of central 5-HT1 and 5-HT2 receptors, a non-selective 5-HT1 and 5-HT2 receptor antagonist, methysergide, was administered 60 min before the 5-HT injection. Pretreatment with methysergide (5 mg/kg i.p. in a volume of 400 microliters) prevented the 5-HT-induced changes in the SS receptor-effector system and in SSLI levels in both brain areas. Methysergide alone had no observable effect on the somatostatinergic system. These results suggest that the frontoparietal cortical and hippocampal somatostatinergic system can be regulated by 5-HT receptors.