D₂‐like dopamine receptor activation excites rat dorsal raphe 5‐HT neurons in vitro

Abstract

The aim of the present study was to investigate the effect of dopamine (DA) on the excitability of dorsal raphe nucleus (DRN) 5-hydroxytryptamine (5-HT) neurons using the patch-clamp technique in brain slices. Bath application of DA (1-300 microM) produced a concentration-dependent membrane depolarization in all 5-HT neurons examined. This effect persisted in the presence of tetrodotoxin (TTX; 1 microM) and low extracellular calcium. Moreover, blockade of ionotropic glutamate receptors with 6,7-dinitroquinoxaline-2,3-dione (DNQX) and 2-amino-5-phosphonopentanoic acid (AP5) did not prevent DA-induced depolarization, indicating that it was mediated by a direct effect of DA on 5-HT neurons. The DA-induced depolarization was not antagonized by selective alpha1-adrenergic receptor antagonists, prazosin and WB 4101, but by a nonselective DA receptor antagonist, haloperidol. In addition, the selective D2-like receptor agonist quinpirole and antagonist sulpiride mimicked and blocked DA-induced depolarization, respectively. These results indicate that DA-induced membrane depolarization in DRN 5-HT neurons is mediated by the activation of D2-like DA receptors. The DA-induced membrane depolarization and inward current were associated with an increase in membrane conductance. Examination of the current-voltage (I-V) relationship for the DA-induced inward current revealed that the amplitude of the current increased with membrane hyperpolarization and reversed polarity at a potential near -15 mV. These data suggest that DA-induced depolarization in DRN 5-HT neurons is not mediated by a decrease in potassium conductance, but most likely by the activation of a nonselective cation current.

Heightened Amygdala Long-Term Potentiation in Neurotensin Receptor Type-1 Knockout Mice

“…Notably, several studies have indicated that pyramidal neurons are excited via activation of D 2 -like receptors (Haj-Dahmane, 2001;Kroner et al, 2005;Yang et al, 1991). Consistent with these reports, we observed that quinpirole elicited small (B3 mV) depolarization of BLA pyramidal neurons (data not shown).…”

Chronic effect of nicotine on serotonin transporter mRNA in the raphe nucleus of rats: Reversal by co‐administration of bupropion

“…48 In addition, a recent electrophysiological study by HajDahmane showed that 5HT neurons in the dorsal raphe were activated by dopamine D2 receptor stimulation. 49 In conclusion, the present study suggests that chronic nicotine administration decreased the expression of 5HTT mRNA, and co-administration of bupropion counteracted this decrease. Although the mechanism of reduced expression of 5HTT or bupropion's prophylactic action was not clear, there might be a close interaction among smoking cessation, development of depression and 5HT function in the brain.…”

A New Class of Antidepressant Drugs in the Treatment of Psychiatric Disorders: The Triple Reuptake Inhibitors

“…On the other and, growing evidence suggest that DA may modulate the activity of 5-HT and NE neurons. It is suspected that DA directly increases the neuronal activity of 5-HT neurons in the DR (Haj-Dahmane, 2001;Martin-Ruiz et al, 2001), thereby enhancing local 5-HT outflow (Ferre et al, 1994;Ferre and Artigas, 1993;Martin-Ruiz et al, 2001). In contrast, multiple source of evidence demonstrates that DA inhibits the neuronal activity of NE neurons in the LC (Guiard et al, 2008a(Guiard et al, , 2008bDeutch et al, 1986;Elam et al, 1986).…”

“…Consequently, triple reuptake inhibitors (TRIs) that simultaneously inhibit the reuptake of the three monoamines 5-HT, NE, DA (Chen & Skolnick, 2007) may provide greater symptomatic relief than SSRIs, NRIs or SNRIs. The interest of TRIs may also rely on the excitatory effect of DA upon the serotonergic system (Haj-Dahmane, 2001;Martin-Ruiz et al, 2001), thus suggesting that an increase in dopaminergic neurotransmission would facilitate that of 5-HT. In accordance with this hypothesis, it was shown that combination of SSRIs with bupropion lead to a synergy on monoamine transmission (Ghanbari et al 2010;Prica et al 2008;Li et al 2002), as well as producing a robust antidepressant effect especially in treatment-resistant depressed patients Fig.…”