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

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.