Acute and Chronic Treatments with Citalopram Lower Somatostatin Levels in Rat Brain Striatum Through Different Mechanisms

• Published in: Journal of neurochemistry Vol. 69; no. 1; pp. 206 - 213
• Main Authors: Prosperini, Elena, Rizzi, Massimo, Fumagalli, Fabio, Tarizzo, Gianluca, Samanin, Rosario, Bendotti, Caterina
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.07.1997; Blackwell
• Subjects: 5‐Hydroxytryptamine uptake inhibitors; Animals; Basal ganglia; Biological and medical sciences; Blotting, Northern; Citalopram; Citalopram - pharmacology; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Dose-Response Relationship, Drug; Male; Medical sciences; Neuropharmacology; Nucleus Accumbens - drug effects; Nucleus Accumbens - metabolism; Obsessive‐compulsive disorder; Pharmacology. Drug treatments; Potassium Chloride - pharmacology; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Sprague-Dawley; RNA, Messenger - metabolism; Serotonin Uptake Inhibitors - pharmacology; Somatostatin; Somatostatin - genetics; Somatostatin - metabolism; Tetrodotoxin - pharmacology; Veratridine - pharmacology; Obsessive compulsive disorder; Intraperitoneal administration; Serotonin; Rat; Acute; Rodentia; Central nervous system; Basal ganglion; Corpus striatum; Reuptake inhibitor; Citalopram; Vertebrata; Chronic; Mammalia; Treatment; Animal; Antidepressant agent; Somatostatin; Mechanism of action; Brain (vertebrata)
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.1997.69010206.x

: The suggestion that somatostatin is involved in the pathophysiology of obsessive‐compulsive disorder and the evidence that selective serotonin reuptake inhibitors show significant antiobsessional effect prompted us to examine the effect of citalopram, a selective and potent serotonin 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 striatum 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 overflow of somatostatin‐like immunoreactivity from striatal slices was significantly increased 1 h after a single injection of citalopram and was still higher, although not significantly, 4 h after the drug injection. Levels of preprosomatostatin mRNA were unchanged in striatum and accumbens 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 striatum but not in other brain regions 24 h after the last dose. No change was found in the basal or K+‐evoked overflow of somatostatin‐like immunoreactivity at 1, 4, and 24 h after the last drug injection. These results suggest that acute and chronic treatment with citalopram reduces somatostatin levels in striatum by different mechanisms. Whereas a single dose of the drug reduces somatostatin levels by increasing the release of the peptide, repeated drug treatment reduces the biosynthesis of somatostatin.