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From Long-term administration of the dopamine D3/2 receptor agonist pramipexole increases dopamine and serotonin neurotransmission in the male rat forebrain:

The sensitivity of postsynaptic D2 receptors in the prefrontal cortex (PFC) remained unaltered following pramipexole administration, as indicated by the unchanged responsiveness to the microiontophoretic application of DA. Their tonic activation was, however, significantly increased by 104% compared with the control level.

What does this mean? How does it enhance DA transmission?

Thanks.

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In physiology, "tonic" refers to something roughly continuous or static.

In terms of receptor activation, tonic typically means there is some small quantity of agonist present such that the receptor is always activated a little bit. The receptors mediating tonic effects are typically "extrasynaptic": outside the synapse, and typically have higher affinity for their agonist. The opposite of tonic would be phasic - where a release of neurotransmitter causes an immediate and brief receptor activation.

In the passage you quote, they try puffing on some DA ("microiontophoretic application of DA") and they get the same response with and without pramipexole, so there is no effect on the phasic response.

However, the tonic activation, when they aren't puffing on DA, was increased. You normally measure this tonic activation by using a receptor antagonist (in this case they use haloperidol). The tonic activation is equal to (without antagonist) - (with haloperidol).

The drug they are using, pramipexole, is a D2 receptor agonist. How I would interpret their result is that, because pramipexole is around all the time during their experiments, there is constant low-level activity at the D2 receptor. They did not find evidence that this low-level activity decreased the response to phasic dopamine release, however; if it did, they would have seen a decreased response when they puffed on DA.


Chernoloz, O., El Mansari, M., & Blier, P. (2012). Long-term administration of the dopamine D3/2 receptor agonist pramipexole increases dopamine and serotonin neurotransmission in the male rat forebrain. Journal of psychiatry & neuroscience : JPN, 37(2), 113–121. doi:10.1503/jpn.110038

Grace, A. A. (2000). The tonic/phasic model of dopamine system regulation and its implications for understanding alcohol and psychostimulant craving. Addiction, 95(8s2), 119-128.

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  • $\begingroup$ Thanks for this informative answer. $\endgroup$ – user155624 Nov 16 at 14:12

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