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

Abstract

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.

In Vivo Evidence that 5-HT2C Receptor Antagonist but not Agonist Modulates Cocaine-Induced Dopamine Outflow in the Rat Nucleus Accumbens and Striatum

“…5-HT 2C receptors and DA outflow S Navailles et al 5-HT 2C receptors may unmask excitatory and phasic influences on DA outflow exerted by endogenous 5-HT via other 5-HT receptors, as already shown in case of concomitant increase in DA and 5-HT transmission (Kankaanpää et al, 2002;Bubar et al, 2003;Porras et al, 2003). Additional experiments are warranted to evaluate this possibility.…”

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

“…Systemic administration of 5-HT3 receptor antagonists (ICS 205-930, ondansetron, or MDL 72222) attenuates the increase in striatal DA release induced by morphine (Porras et al, 2003) and ethanol (Wozniak et al, 1990), but not haloperidol, amphetamine or cocaine (Porras et al, 2003). Also, pretreatment with the 5-HT3 receptor antagonist ondansetron did not affect haloperidolinduced activation of DA turnover in the striatum (Koulu et al, 1989).…”

“…Porras et al (2003) suggested that 5-HT3 receptors only modulate nigrostriatal release when the stimulated DA release is depolarization-dependent and both DA and 5-HT tones are both elevated. When haloperidol was coadministered with a SSRI known to elevate 5-HT tone, the resulting increase in DA release was attenuated by 5-HT3 receptor antagonism, supporting the authors' theory for selective modulation (Porras et al, 2003).…”

“…It has been shown, however, that intrastriatal 5-HT3 antagonism (ICS 205930, MDL 72222 or ondansetron) can attenuate induced increases in striatal DA, suggesting that at least a portion of the relevant receptors may be striatal (Benloucif et al, 1993;Porras et al, 2003).…”

Administração prolongada do ácido 13-cis-retinóico (isotretinoína) em camundongos machos adolescentes: comportamentos emocionais e quantificação de transcritos de componentes do sistema serotoninérgico central.

“…Estudos farmacológicos evidenciaram a possibilidade deste receptor modular diretamente, ou indiretamente, a atividade neuronal de outros sistemas, tais como dopaminérgicos, colinérgicos e gabaérgicos (Díez-Ariza et al, 1998;Porras et al, 2003).…”