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Differential neurochemical properties of central serotonergic transmission in Roman high‐ and low‐avoidance rats

The selective breeding of Roman high‐ (RHA/Verh) and low‐avoidance (RLA/Verh) rats for rapid versus poor acquisition of active avoidant behaviour has produced two behavioural phenotypes with different performances in a variety of animal models of anxiety, in which RLA/Verh rats are consistently more fearful than RHA/Verh rats. In addition, these two lines display different functional properties of brain neurotransmitters like serotonin (5‐HT), known to be involved in the expression of anxiety‐ and depression‐related behaviours. Therefore, we used brain microdialysis and [3H]‐citalopram binding autoradiography to characterize further the neurochemical properties of 5‐HTergic transmission in the two lines. No significant line‐related differences were detected in the basal 5‐HT output in the frontoparietal cortex (FPCx). In contrast, the increase in the cortical 5‐HT output elicited by the systemic administration or the local application, via reverse dialysis, of chlorimipramine and fluoxetine was more robust in RHA/Verh than in RLA/Verh rats. Moreover, the binding signal of [3H]‐citalopram to 5‐HT re‐uptake sites was more intense in the FPCx of RHA/Verh rats than in their RLA/Verh counterparts. These findings suggest that the functional tone of the 5‐HTergic projection to the FPCx is stronger in the RHA/Verh line relative to the RLA/Verh line. It is proposed that RLA/Verh rats may be used as a model with heuristic value for studying the role of 5‐HTergic transmission in anxiety and in the anxiolytic effects of monoamine re‐uptake inhibitors.