Modulation of inhibitory transmission by dopamine in rat basal forebrain nuclei: activation of presynaptic D1-like dopaminergic receptors.
The effects of dopamine (DA) on inhibitory transmission onto identified magnocellular neurons were examined in rat basal forebrain slices using whole-cell recording. IPSCs evoked by focal stimulation within basal forebrain nuclei were reversibly blocked by 10 microM bicuculline and had a decay time constant of 20.1 +/- 0.77 msec in the presence of 6-cyano-7-nitroquinoxalline-2,3-dione (5 mM). Bath application of DA reduced the amplitude of IPSCs up to 71.1 +/- 1.49% in a concentration-dependent manner between 0.003 and 1 mM (the IC50 value being 6.6 microM), without any effect on the holding current at -70 mV. DA (10 microM) reduced the frequency of miniature IPSCs (mIPSCs) recorded in the presence of TTX (0.5 microM), without affecting their mean amplitude, rise time, and decay time constant. Furthermore, the DA-induced effect on mIPSCs remained unaffected by 100 microM cadmium, suggesting a presynaptic mechanism independent of calcium influx. SKF 81297, a D1-like agonist, mimicked DA-induced effect on evoked IPSCs (IC50, 10.9 microM), whereas R(-)-TNPA or (-)-quinpirole, D2-like agonists (30 microM), had little or no effect on the amplitude of evoked IPSCs. R(+)-SCH 23390, a D1-like antagonist, antagonized the DA-induced effect on IPSCs (K(B) 0.82 microM), whereas S(-)-eticlopride, a D2-like antagonist, showed slight antagonism (K(B) 7.8 microM). Forskolin (10 microM) reduced the amplitude of evoked IPSCs to approximately 58% of the control and occluded the inhibitory effect of DA. These findings indicate that DA reduces inhibitory transmission onto magnocellular basal forebrain neurons by activating presynaptic D1-like receptors.
Momiyama
T
T
Department of Pharmacology, University College London, United Kingdom.
Sim
J A
JA
D000818:Animals; D004298:Dopamine / Q000494:pharmacology*; D004553:Electric Conductivity; D009433:Neural Inhibition; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D016548:Prosencephalon / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D017447:Receptors, Dopamine D1; D005680:gamma-Aminobutyric Acid; D004298:Dopamine