Lorcaserin, which is a selective agonist of serotonin2C receptors (5-HT2CRs), is a
new FDA-approved anti-obesity drug that has also shown therapeutic promise in other
brain disorders, such as addiction and epilepsy. The modulation of dopaminergic function
might be critical in the therapeutic effect of lorcaserin, but its exact effect is
unknown. Here, we studied the effect of the peripheral administration of lorcaserin
on the ventral tegmental area (VTA), the substantia nigra pars compacta (SNc) dopaminergic
neural activity, dopamine (DA) dialysis levels in the nucleus accumbens and striatum
and on DA tissue levels in 29 different rat brain regions. Lorcaserin (5-640 μg/kg,
i.v.) moderately inhibited only a subpopulation of VTA DA neurons, but had no effect
on the SNc neurons. Lorcaserin (0.3, 3 mg/kg, i.p.) did not change VTA and SNc DA
population neural activity but slightly decreased the firing rate and burst firing
of the spontaneously active VTA neurons, without altering DA extracellular dialysate
levels in both the nucleus accumbens and the striatum. Quantitative analysis of DA
and metabolites tissue contents of the 29 areas studied revealed that lorcaserin (0.3
or 3 mg/kg, i.p.) only affected a few brain regions, i.e., increased DA in the central
amygdala, ventral hypothalamus and nucleus accumbens core and decreased it in the
ventromedial striatum. On the other hand, lorcaserin dramatically changed the direction
and reduced the number of correlations of DA tissue content among several brain areas.
These effects on DA terminal networks might be significant in the therapeutic mechanism
of lorcaserin. This article is part of the special issue entitled 'Serotonin Research:
Crossing Scales and Boundaries'.