**Introduction**
Ageing is negatively correlated with physical activity (PA) and this has an undesirable impact on overall health(1). The neurotransmitter serotonin (5-HT) is known to be inversely correlated with physical activity(2). Here we investigate a serotonergic neuronal circuit involved in voluntary physical activity during ageing in mice.
**Methods**
We injected designed DREADD proteins (Designer Receptors Exclusively Activated by Designer Drugs) that enable non-invasive control of neuronal signalling through the  Gq (hMD3q, excitatory) and Gi (hMD4i) G-protein coupled signalling pathways in the dorsal raphe nucleus (DRN) of Tph2iCre mice (tph2, rate-limiting enzyme in 5HT synthesis) to modulate 5-HT release, or in the ventral segmental area (VTA) of 5-HT2CRCre mice (5-HT type 2c receptor) to modulate activity in a 5-HT target region. Upon administration of CNO (clozapine-N-Oxide, Designer drug for DREADD) (1mg/kg, IP) and lorcaserin (3mg/kg, IP) we characterised the locomotor activity profile of all mice using TSE Phenomaster.
**Results**
Our results showed that activation of Tph2DRN cells reduced PA (p<0.05; Veh, n=11, 12811±1554 vs CNO, n=10 8196±2821, t=2.507,df=19, ) while its inhibition induced locomotion (p<0.001; Veh, n=5, 13209±1181, vs CNO, n=5, 26948±2515, t=4.944, df=8. Chemogenetic activation of 5-HT2CRVTA reduced PA (p<0.05, Veh, n=6, 6650±1329 vs CNO, n=9, 3587±401, t=2.606, df=13) while its inhibition reverted the effects of lorcaserin (p<0.01, Lorc+veh n=6, 10704±1235 vs Lorc+CNO n=9, 16280±1405, t=2.930, df=11)
**Conclusion**
In summary, our data indicate that the serotonin system through the 5-HT2cR signalling in the VTA is involved in the control of locomotion and identify a means to reverse age-related decline in physical activity.

Role of brain serotonin in age-related decline in physical activity in mice

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