Influence of fluoxetine and p-chloroamphetamine on the somatostatin receptor–adenylyl cyclase system in the rat frontoparietal cortex

Abstract

There is evidence that suggests a reciprocal functional link between the serotonergic and the somatostatinergic system in the rat Ž . frontoparietal cortex. However, to date, the role of endogenous 5-hydroxytryptamine serotonin on the regulation of the somatostatin Ž .Ž . Ž . SS receptor-adenylyl cyclase AC system remains unclear. In the present study, the administration of fluoxetine 10 mgrkg i.p. , a w 125 x 11 5-hydroxytryptamine uptake inhibitor in a single dose or administered daily for 14 days increased the number of specific I Tyr -SS receptors, with no change in the receptor affinity, in rat frontoparietal cortical membranes. However, the capacity of SS to inhibit Ž . forskolin FK -stimulated AC activity in these membranes was lower than in the control groups. The ability of the stable GTP analogue X Ž Ž . . 5 -guanylylimidodiphosphate Gpp NH p to inhibit FK-stimulated AC activity in frontoparietal cortical membranes was also decreased in Ž . rats acutely and chronically treated with fluoxetine. p-Chloroamphetamine 5 mgrkg i.p. , which leads to a lasting reduction of 5-hydroxytryptamine innervation, administered on days 1, 3 and 5 and the rats sacrificed 1 or 3 weeks after the first injection, decreased the number of SS receptors without changing the receptor affinity. In this experimental group, SS also caused a significantly lower Ž . inhibition of FK-stimulated AC activity. p-Chloroamphetamine had no effect on the ability of Gpp NH p to inhibit FK-stimulated AC activity in frontoparietal cortical membranes at all the time periods studied. The present results suggest that under normal circumstances some SS receptors are under a tonic stimulatory control through the serotonergic system. q 1997 Elsevier Science B.V.