Conditional involvement of striatal serotonin3 receptors in the control of in vivo dopamine outflow in the rat striatum

Grégory Porras, Philippe De Deurwaerdère, Delphine Moison, Umberto Spampinato
European Journal of Neuroscience. 2003-02-01; 17(4): 771-781
DOI: 10.1046/j.1460-9568.2003.02512.x

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Serotonin3 (5-HT3) receptors can affect motor control through an interaction with
the nigrostriatal dopamine (DA) neurons, but the neurochemical basis for this
interaction remains controversial. In this study, using in vivo microdialysis, we
assessed the hypothesis that 5-HT3 receptor-dependent control of striatal DA
release is conditioned by the degree of DA and/or 5-HT neuron activity and the
means of DA release (impulse-dependent vs. impulse-independent). The different
DA-releasing effects of morphine (1 and 10 mg/kg), haloperidol (0.01 mg/kg),
amphetamine (1 and 2.5 mg/kg), and cocaine (10 and 20 mg/kg) were studied in the
striatum of freely moving rats administered selective 5-HT3 antagonists
ondansetron (0.1 mg/kg) or MDL 72222 (0.03 mg/kg). Neither of the 5-HT3
antagonists modified basal DA release by itself. Pretreatment with ondansetron or
MDL 72222 reduced the increase in striatal DA release induced by 10 mg/kg
morphine but not by 1 mg/kg morphine, haloperidol, amphetamine or cocaine. The
effect of 10 mg/kg morphine was also prevented by intrastriatal ondansetron (1
microm) administration. Reverse dialysis with ondansetron also reduced the
increase in DA release induced by the combination of haloperidol and the 5-HT
reuptake inhibitor citalopram (1 mg/kg). Considering the different DA and
5-HT-releasing properties of the drugs used, our results demonstrate that
striatal 5-HT3 receptors control selectively the depolarization-dependent
exocytosis of DA only when central DA and 5-HT tones are increased concomitantly.

Auteurs Bordeaux Neurocampus