Presynaptic dopamine D₂‐like receptors inhibit excitatory transmission onto rat ventral tegmental dopaminergic neurones

Abstract

The effects of dopamine (DA) on non‐NMDA glutamatergic transmission onto dopaminergic neurones in the ventral tegmental area (VTA) were examined in rat midbrain slices using the whole‐cell patch‐clamp technique. EPSCs in dopaminergic neurones evoked by focal stimulation within the VTA were reversibly blocked by 5 μM CNQX in the presence of bicuculline (20 μM), strychnine (0.5 μM) and D‐amino‐5‐phosphonopentanoic acid (D‐AP5, 25 μM). Bath application of DA reduced the amplitude of EPSCs up to 65.1 ± 9.52% in a concentration‐dependent manner between 0.3‐1000 μM (IC50, 16.0 μM) without affecting the holding current at −60 mV measured using a Cs+‐filled electrode. The effect of DA on evoked EPSCs was mimicked by the D2‐like receptor agonist quinpirole but not by the D1‐like receptor agonist SKF 81297, and was antagonized by the D2‐like receptor antagonist sulpiride (KB, 0.96 μM), but not by the D1‐like receptor antagonist SCH 23390 (KB, 228.6 μM). Dopamine (30 μM) reduced the mean frequency of spontaneous miniature EPSCs (mEPSCs) without affecting their mean amplitude, and the DA‐induced effect on the mEPSCs was dependent on the external Ca2+ concentration. These results suggest that afferent glutamatergic fibres which terminate on VTA dopaminergic neurones possess presynaptic D2‐like receptors, activation of which inhibits glutamate release by reducing Ca2+ influx.

Cocaine Enhances NMDA Receptor-Mediated Currents in Ventral Tegmental Area Cells via Dopamine D5Receptor-Dependent Redistribution of NMDA Receptors

“…1 B), it seems that the effect of cocaine on NMDAR EPSCs is the sum of differ- ent effects on glutamate neurotransmission elicited by cocaine. Thus, the delay in cocaine-induced potentiation of NMDAR EPSCs could be a result of the previously reported presynaptic inhibition of glutamate release mediated either by DA D 2 receptors (Koga and Momiyama, 2000) or 5-hydroxytryptamine (5-HT) 2 receptors (Jones and Kauer, 1999). This raised the possibility that, initially, the effect of cocaine on NMDAR EPSCs is masked by inhibition of glutamate release, an effect that wanes as NMDAR currents grow stronger.…”

“…However, as mentioned above, more recent studies have reported that both presynaptic serotonin and dopamine receptors can reduce glutamate synaptic transmission in the VTA (Jones and Kauer, 1999;Koga and Momiyama, 2000). Other studies suggest that D 1 -like receptor stimulation in the VTA leads to a delayed increase of extracellular glutamate, although the increase in glutamate was not attributable to synaptic spillover (Wolf andXue, 1998, Wolf et al, 2000).…”

Theanine, γ-glutamylethylamide, a unique amino acid in tea leaves, modulates neurotransmitter concentrations in the brain striatum interstitium in conscious rats

“…In addition, some studies suggested that dopamine could modify glutamate neurotransmission. (Moghaddam et al 1990;Yadid et al 1993;Koga and Momiyama 2000). Because the chemical structure of theanine is similar to glutamic acid, some studies of theanine examined its relationship to glutamic acid function and metabolism (Sugiyama et al 2003;Kakuda et al 2002a;Tsuge et al 2003;Oda et al 1980); however, the glutamate receptor antagonist MK-801 did not affect the increase of dopamine concentration by theanine injection in the rat striatum (Yokogoshi et al 1998a).…”

Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment

“…Conversely, the glutamate system is inhibited by dopamine and facilitated by the inhibition of D 2 receptors. D 2 receptors on glutamatergic fibers in the VTA inhibit glutamate release, while D 2 antagonists reverse this inhibition (Koga & Momiyama, 2000). D 2 receptors also reduce glutamate receptor-mediated activity in the corticostriatal and thalamostriatal pathways, while D 2 antagonists increase the activity (Cepeda et al, 2001).…”

“…Dopamine and glutamate are involved in the same neuronal circuits and influence each other's activity and release of neurotransmitter (Morari et al, 1998). Generally, D 2 receptor agonists decrease the activity of the glutamate system, whereas D 2 antagonists increase the activity (Cepeda et al, 2001;Koga & Momiyama, 2000;Yamamoto & Davy, 1992). Dopamine neurons emanate from two areas in the mid-brain, the substantia nigra and the VTA.…”