ACUTE AND CHRONIC TREATMENTS WITH CITALOPRAM LOWER SOMATOSTATIN LEVELS IN RAT-BRAIN STRIATUM THROUGH DIFFERENT MECHANISMS

The suggestion that somatostatin is involved in the pathophysiology of obsessive-compulsive disorder and the evidence that selective seroton in reuptake inhibitors show significant antiobsessional effect prompte d us to examine the effect of citalopram, a selective and potent serot onin reuptake inhibitor, on the somatostatinergic system in different brain regions of the rat. A single intraperitoneal injection of 10 mg/ kg citalopram significantly reduced somatostatin levels in the striatu m and nucleus accumbens after 4 but not 1, 8, or 24 h. No changes were found in hippocampus. In addition, we found that the K+-evoked overfl ow of somatostatin-like immunoreactivity from striatal slices was sign ificantly increased 1 h after a single injection of citalopram and was still higher, although not significantly, 4 h after the drug injectio n. Levels of preprosomatostatin mRNA were unchanged in striatum and ac cumbens 1 and 4 h after a single drug administration. In rats treated with citalopram (10 mg/kg i.p.) twice daily for 14 days, the levels of somatostatin and its mRNA were significantly decreased in the striatu m but not in other brain regions 24 h after the last dose. No change w as found in the basal or K+-evoked overflow of somatostatin-like immun oreactivity at 1, 4, and 24 h after the last drug injection. These res ults suggest that acute and chronic treatment with citalopram reduces somatostatin levels in striatum by different mechanisms. Whereas a sin gle dose of the drug reduces somatostatin levels by increasing the rel ease of the peptide, repeated drug treatment reduces the biosynthesis of somatostatin.