INFLUENCE OF FLUOXETINE AND P-CHLOROAMPHETAMINE ON THE SOMATOSTATIN RECEPTOR-ADENYLYL CYCLASE SYSTEM IN THE RAT FRONTOPARIETAL CORTEX

There is evidence that suggests a reciprocal functional link between t he serotonergic and the somatostatinergic system in the rat frontopari etal cortex. However, to date, the role of endogenous 5-hydroxytryptam ine (serotonin) on the regulation of the somatostatin (SS) receptor-ad enylyl cyclase (AC) system remains unclear. In the present study, the administration of fluoxetine (10 mg/kg i.p.), a 5-hydroxytryptamine up take inhibitor in a single dose or administered daily for 14 days incr eased the number of specific [I-125]Tyr(11)-SS receptors, with no chan ge in the receptor affinity, in rat frontoparietal cortical membranes. However, the capacity of SS to inhibit forskolin (FK)-stimulated AC a ctivity in these membranes was lower than in the control groups. The a bility of the stable GTP analogue 5'-guanylylimidodiphosphate (Gpp(NH) p) to inhibit FK-stimulated AC activity in frontoparietal cortical mem branes was also decreased in rats acutely and chronically treated with fluoxetine. p-Chloroamphetamine (5 mg/kg i.p.), which leads to a last ing reduction of 5-hydroxytryptamine innervation, administered on days 1, 3 and 5 and the rats sacrificed 1 or 3 weeks after the first injec tion, decreased the number of SS receptors without changing the recept or affinity. In this experimental group, SS also caused a significantl y lower inhibition of FK-stimulated AC activity. p-Chloroamphetamine h ad no effect on the ability of Gpp(NH)p to inhibit FK-stimulated AC ac tivity in frontoparietal cortical membranes at all the time periods st udied. The present results suggest that under normal circumstances som e SS receptors are under a tonic stimulatory control through the serot onergic system. (C) 1997 Elsevier Science B.V.