Functional regulation by dopamine receptors of serotonin release from the rat hippocampus: in vivo microdialysis study

Abstract

The functional regulation by dopamine (DA) receptors of serotonin (5-HT) release from the rat hippocampus was investigated by use of in vivo microdialysis. Dialysate 5-HT levels were reduced by co-perfusion of 10 microM tetrodotoxin (TTX) and were elicited by K+ (60 and 120 mM) stimulation in a concentration-dependent manner. Local perfusion (10 microM) and peripheral administration (20 mg/kg, i.p.) of fluoxetine produced increases in 5-HT levels. These results indicate that the spontaneous 5-HT levels in the rat hippocampus can be used as indices of neuronal origin from the serotonergic nerve terminals. The nonselective dopamine (DA) receptor agonist apomorphine (1, 10 and 100 microM), when perfused through the probe over a period of 40 min, increased 5-HT release in a concentration-dependent manner. Apomorphine-induced (100 microM) increases in 5-HT release was abolished by pretreatment with the selective D2 receptor antagonist, S(-)-sulpiride (1 and 10 microM), but not prevented by pretreatment with the selective D1 receptor antagonist, R(+)-SCH-23390 (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2, 3, 4, 5-tetrahydro-1H-3-benzazepine) (1 microM). S(-)-Sulpiride and R(+)-SCH-23390 by themselves did not alter the spontaneous 5-HT levels. The 5-HT release was elevated by perfusion of the selective DA reuptake inhibitor GBR 12909 (1-[2-[bis(4-fluorophenyl) methoxy]ethyl]-4-[3-phenyl-propyl]piperazine) (1, 10 and 100 microM), indicating the possibility of not only exogenous but also endogenous DA-mediated facilitatory effects on 5-HT release in vivo. The 5-HT release was also elevated by perfused (+/-)-PPHT ((+/-)-2-(N-phenylethyl-N-propyl)-amino-5-hydroxytetralin) (1, 10 and 100 microM), the selective D2 receptor agonist, in a concentration-dependent manner. On the other hand, (+/-)-PPHT (100 microM) failed to increase 5-HT release in catecholamine (CA)-lesioned rats pretreated with 6-hydroxydopamine (6-OHDA)(200 micrograms/rat, i.c.v.). The (+/-)-PPHT-induced (100 microM) increase in 5-HT release was prevented not only by pretreatment with 10 microM S(-)-sulpiride but also by pretreatment with the alpha 2-adrenoceptor antagonist idazoxan (10 microM). These findings suggest that the functional regulation of 5-HT release via D2 receptors exists in the rat hippocampus. Furthermore our results indicate that the facilitatory effect of 5-HT release via D2 receptors may be mediated indirectly by noradrenergic neurons, but not mediated directly through D2 receptors located on serotonergic nerve terminals.

D2-Like Dopamine Receptors Depolarize Dorsal Raphe Serotonin Neurons through the Activation of Nonselective Cationic Conductance

“…These anatomical results suggest that DA input to the DR may play a critical role in the regulation of the function of DR 5-HT neurons. Consistent with this notion, in vivo neurochemical studies have reported that administration of DA receptor agonists increases the synthesis and release of 5-HT in the DR (Ferré et al, 1994;Matsumoto et al, 1996). Direct evidence for a role of DA in the regulation of 5-HT neurons function comes from recent in vitro electrophysiological study showing that activation of DA receptors induces a membrane depolarization and thereby increases the excitability of DR 5-HT neurons (Haj-Dahmane, 2001).…”

Opponency Revisited: Competition and Cooperation Between Dopamine and Serotonin

“…Much less data exist as to whether DA exerts regulation over 5-HT release, and it is not clear whether this regulation would be excitatory or inhibitory (Ferré et al, 1994;Matsumoto et al, 1996;Ferré and Artigas, 1993;Thorré et al, 1998). This could be taken as evidence for a hierarchical arrangement between 5-HT and DA, with the former exerting its effects by manipulating the latter.…”

Temperament and arousal systems: A new synthesis of differential psychology and functional neurochemistry

“…Activation of 5-HT2A and 5-HT3 receptors, via mediation by GABA neurons, inhibits the release of prefrontal neocortical DA, however activation of 5-HT3 receptors also increases DA release in the nucleus accumbens and the medial prefrontal cortex (mPFC) (Di Matteo et al, 2008;Fink & Göthert, 2008). DA also regulates 5-HT through projections from DA nuclei to the dorsal raphé nucleus (DR), by DA neurones within the DR or more indirectly, via action of D2 receptors on NA neurons (Matsumoto et al, 1996;Adell et all, 2010).…”