Serotonin reuptake inhibition by citalopram in rat strains differing for their emotionality.
Acute administration of the selective serotonin (5-HT) reuptake inhibitor (SSRI), citalopram (1-10 mg/kg, i.p. 1 h before an elevated plus-maze test), to Spontaneously Hypertensive rats (SHRs), Lewis (LEW) rats, and Wistar-Kyoto (WKY) rats, i.e., rat strains differing for their emotionality, promoted anxiety, and/or hypoactivity, except in WKY rats. In the three strains, such a pretreatment increased central 5-HT levels and/or decreased 5-hydroxyindoleacetic acid levels. Hippocampal, but not midbrain or striatal, [3H]citalopram binding at 5-HT transporters was lower in WKY rats than in SHRs. However, neither [3H]5-HT reuptake kinetics nor the potencies of citalopram (1-1000 nM) to inhibit [3H]5-HT reuptake into hippocampal and striatal synaptosomes differed between strains. This was confirmed in vivo by means of microdialysis in the hippocampus of freely moving rats. Thus, although LEW rats displayed a 3-4 fold higher baseline level of extracellular 5-HT in the hippocampus, compared with SHRs and WKY rats, local perfusion with 1 microM citalopram promoted relative increases in extracellular 5-HT levels over baseline that were similar in all strains. Lastly, acute i.p. administration of 3.3 mg/kg citalopram (1 h beforehand) decreased to similar extents [3H]5-HT reuptake into hippocampal synaptosomes from SHRs and WKY rats. This study indicates that genetic differences in the behavioural responses to SSRIs may involve 5-HT transporter-independent mechanisms.
Pollier
F
F
Laboratory of NeuroGénétique and Stress, INSERM U471, Bordeaux, France.
Sarre
S
S
Aguerre
S
S
Ebinger
G
G
Mormède
P
P
Michotte
Y
Y
Chaouloff
F
F
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D015283:Citalopram / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004644:Emotions / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D017551:Microdialysis; D009928:Organ Specificity; D051381:Rats; D011917:Rats, Inbred Lew; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013045:Species Specificity
D015283:Citalopram; D006897:Hydroxyindoleacetic Acid; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors