Altered neuronal activity and differential sensitivity to acute antidepressants of locus coeruleus and dorsal raphe nucleus in Wistar Kyoto rats: a comparative study with Sprague Dawley and Wistar rats

Abstract

The Wistar Kyoto rat (WKY) has been proposed as an animal model of depression. The noradrenergic nucleus, locus coeruleus (LC) and the serotonergic nucleus, dorsal raphe (DRN) have been widely implicated in the ethiopathology of this disease. Thus, the goal of the present study was to investigate in vivo the electrophysiological properties of LC and DRN neurons from WKY rats, using single-unit extracellular techniques. Wistar (Wis) and Sprague Dawley (SD) rats were used as control strains. In the LC from WKY rats the basal firing rate was higher than that obtained in the Wis and SD strain, and burst firing activity also was greater compared to that in Wis strain but not in SD. The sensitivity of LC neurons to the inhibitory effect of the α2-adrenoceptor agonist, clonidine and the antidepressant reboxetine was lower in WKY rats compared to Wis, but not SD. Regarding DRN neurons, in WKY rats burst activity was lower than that obtained in Wis and SD rats, although no differences were observed in other firing parameters. Interestingly, while the sensitivity of DRN neurons to the inhibitory effect of the 5-HT1A receptor agonist, 8-OH-DPAT was lower in the WKY strain, the antidepressant fluoxetine had a greater inhibitory potency in this rat strain compared to that recorded in the Wis group. Overall, these results point out important electrophysiological differences regarding noradrenergic and serotonergic systems between Wis and WKY rats, supporting the utility of the WKY rat as an important tool in the research of cellular basis of depression