Long-term administration of citalopram reduces basal and stress-induced extracellular noradrenaline levels in rat brain.
BACKGROUND
Panic disorders are commonly treated with selective serotonin reuptake inhibitors (SSRIs). However, the effect of SSRIs on noradrenaline systems in the brain has not been fully elucidated at the present time.


OBJECTIVE
The effects of long-term administration of citalopram, an SSRI, on basal as well as stress-induced extracellular noradrenaline levels in the basolateral nucleus of the amygdala (BLA) and the locus coeruleus (LC) were determined. In addition, the responsiveness of noradrenaline transporters and alpha2-adrenoceptors were determined after long-term administration of citalopram.


METHODS
Brain microdialysis was used to assess the extracellular levels of noradrenaline in conscious rats. Desipramine and clonidine were used to functionally evaluate the noradrenaline transporter and alpha2-adrenoreceptor, respectively.


RESULTS
In rats treated daily for 14 days with citalopram (10 mg kg(-1) day(-1) s.c.), dialysate noradrenaline levels showed remarkable decreases in both the BLA and the LC to about 25 and 45% of controls, respectively. The stress-induced increase of noradrenaline was almost completely abolished in the BLA, but was relatively stable in the LC. The effect of local application of desipramine tended to be suppressed only in the LC. The effect of local application of clonidine was enhanced only in the BLA.


CONCLUSIONS
The present results indicate that chronic administration of citalopram strongly decreases the extracellular levels of noradrenaline in the brain. The anti-panic effect of citalopram might be due to sensitization of the alpha2-adrenoceptors leading to suppression of the stress response through noradrenergic activity. This mechanism is specific for the BLA.
Kawahara
Yukie
Y
Department of Pharmacology, Kurume University School of Medicine, Kurume 830 0011, Japan. yukikawa@med.kurume-u.ac.jp
Kawahara
Hiroshi
H
Kaneko
Fumi
F
Tanaka
Masatoshi
M
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D000679:Amygdala / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D019540:Area Under Curve; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015283:Citalopram / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology*; D003000:Clonidine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D015314:Dialysis Solutions / Q000737:chemistry; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D007279:Injections, Subcutaneous; D008125:Locus Coeruleus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017551:Microdialysis / Q000379:methods; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D013315:Stress, Psychological / Q000503:physiopathology; D013997:Time Factors
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D015283:Citalopram; D003000:Clonidine; D015314:Dialysis Solutions; D009638:Norepinephrine; D017367:Selective Serotonin Reuptake Inhibitors