5-HT1A receptor antagonism decreases motor activity and influences dopamine and serotonin metabolization pathways, primarily in cingulate cortex and striatum

We assessed the effect of the 5-HT_1A receptor (R) antagonist WAY100,635 on motor behaviors, object place learning and the regional levels of dopamine (DA), serotonin (5-HT) and their metabolites in the rat brain. After a single dose of either WAY100,635 (0.4 mg/kg) or vehicle (0.9% NaCl), recognition memory was assessed together with motor/exploratory behaviors. After sacrifice, regional DA, 5-HT and metabolite levels were determined with HPLC. Overall activity and exploratory behavior were reduced by WAY100,635. Object place recognition did not differ between treatments. WAY100,635 promoted DA metabolization (1) by both monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT) in cingulate, caudateputamen, thalamus and cerebellum, (2) solely by MAO in dorsal hippocampus and (3) solely by COMT in ventral hippocampus and brainstem, but suppressed DA metabolization (by both MAO and COMT) in nucleus accumbens. It promoted 5-HT metabolization (by MAO) in cingulate, caudateputamen, dorsal hippocampus and brainstem, but suppressed it in nucleus accumbens, thalamus and cerebellum. WAY100,635 altered activity and exploratory behavior as well as the quantitative relations between the neurotransmitter/metabolite levels in the individual brain regions, by inducing region-specific shifts in the metabolization pathways.