Concentration-dependent actions of stimulated dopamine release on neuronal activity in rat striatum

Voltammetric analysis was combined with single unit recording to measure the effects of endogenous dopamine, released by electrical stimulation of the median forebrain bundle, on neuronal activity in the rat striatum in vivo. Fast differential ramp voltammetry, a more sensitive form of fast cyclic voltammetry, was used to measure extracellular dopamine levels during a 50-ms scan epoch every 500 ms. Using the same carbon fibre microelectrode, neuronal activity was recorded in between the electrochemical epochs. A steady-state electrochemical signal equivalent to about 100 nM dopamine was seen in the unstimulated striatum. The responses of 122 striatal units to stimulated dopamine release were recorded in 37 acute experiments. Ninety-one units which displayed a large spike amplitude (greater than or equal to 50 microV) were recorded during stimulated release of dopamine initially to levels of between 100 and 500 nM. The majority (49) showed a profound excitation, 23 showed inhibition, and nine units gave complex responses. Only 10 units were unresponsive. All the responses of these large units outlasted the transient increase in dopamine levels, often for more than 1 min. In contrast, all the 31 units which displayed a small spike amplitude (less than 50 microV) were powerfully activated by dopamine release within this range. Administration of alpha-methyl-para-tyrosine (250 mg/kg i.p.) abolished both dopamine release and the response of the five large units and four small units examined, indicating that the neuronal response was directly attributable to dopamine. Dopamine release was increased by increasing the stimulus duration over the range 0.25-10 s. With increasing levels of dopamine release the excitatory response of large units rose to a maximum and then decreased until it was eventually transformed entirely into an inhibition at dopamine levels above 1 microM. In contrast, the excitatory response of small units always increased in magnitude with increasing dopamine release to levels greater than 1 microM. The large units that showed inhibition at low levels of dopamine were also inhibited at high levels. Tail-pinch stimuli excited 21/23 large units and all seven small units tested, although this stimulus did not evoke a detectable rise in dopamine levels. We suggest that the fundamental action of dopamine in the striatum is excitation, whether involving D1 or D2 receptors. The small units described here could be inhibitory interneurons which convert the excitatory response of large units into inhibition. Dopamine may regulate striatal function by enhancing particular input-output pathways while also activating lateral inhibitory mechanisms serving to "gate-out" alternative outputs.