Differences in Anxiety-Like Behavior within a Batch of Wistar Rats Are Associated with Differences in Serotonergic Transmission, Enhanced by Acute SRI Administration, and Abolished By Serotonin Depletion

作者：Naslund Jakob; Studer Erik; Pettersson Robert; Hagsater Melker; Nilsson Staffan; Nis**randt Hans; Eriksson Elias^*

来源：International Journal of Neuropsychopharmacology, 2015, 18(8).

DOI：10.1093/ijnp/pyv018

• Serotonin
• anxiety
• serotonin reuptake inhibitors
• tryptophan hydroxylase 2
• elevated plus maze

Background: The anxiety-reducing effect of long-term administration of serotonin reuptake inhibitors is usually seen only in subjects with anxiety disorders, and such patients are also abnormally inclined to experience a paradoxical anxietyenhancing effect of acute serotonin reuptake inhibition. These unique responses to serotonin reuptake inhibitors in anxietyprone subjects suggest, as do genetic association studies, that inter-individual differences in anxiety may be associated with differences in serotonergic transmission.
Methods: The one-third of the animals within a batch of Wistar rats most inclined to spend time on open arms in the elevated plus maze were compared with the one-third most inclined to avoid them with respect to indices of brain serotonergic transmission and how their behavior was influenced by serotonin-modulating drugs.
Results: "Anxious" rats displayed higher expression of the tryptophan hydroxylase-2 gene and higher levels of the tryptophan hydroxylase-2 protein in raphe and also higher levels of serotonin in amygdala. Supporting these differences to be important for the behavioral differences, serotonin depletion obtained by the tryptophan hydroxylase-2 inhibitor p-chlorophenylalanine eliminated them by reducing anxiety in "anxious" but not "non-anxious" rats. Acute administration of a serotonin reuptake inhibitor, paroxetine, exerted an anxiety-enhancing effect in "anxious" but not "non-anxious" rats, which was eliminated by long-term pretreatment with another serotonin reuptake inhibitor, escitalopram.
Conclusions: Differences in an anxiogenic impact of serotonin, which is enhanced by acute serotonin reuptake inhibitor administration, may contribute to differences in anxiety-like behavior amongst Wistar rats.

• 出版日期2015-6