[6] The D5 subtype is a G-protein coupled receptor, which promotes synthesis of cAMP by adenylyl cyclase via activation of Gαs/olf family of G proteins.

[9] Activation of D5 receptors is shown to promote expression of brain-derived neurotrophic factor and increase phosphorylation of protein kinase B in rat and mice prefrontal cortex neurons.

[10] In vitro, D5 receptors show high constitutive activity that is independent of binding any agonists.

[14] It is found in neurons in amygdala, frontal cortex, hippocampus, striatum, thalamus, hypothalamus, basal forebrain, cerebellum,[14] and midbrain.

[15] Dopamine receptor D5 is exclusively expressed by large aspiny neurons in neostriatum of primates, which are typically cholinergic interneurons.

[22] D5 receptors may be required for long-term potentiation at the synapse between medial perforant path and dentate gyrus in murine hippocampal formation.

[24] Polymorphisms in the DRD5 gene, which encodes dopamine receptor D5, have been suggested to play a role in the initiation of smoking.

[27] In a rat model of ADHD, low density of D5 was found in the hippocampal pyramidal cell somas.

[28] D5 receptors may be involved in burst firing of subthalamic nucleus neurons in 6-OHDA rat model of Parkinson's disease.

In this animal model, blockage of D5 receptors with flupentixol reduces burst firing and improves motor deficits.

Mice lacking this receptor in their brains showed hypertension and elevated blood pressure, which may have been caused by increased sympathetic tone.

The expression of D5 receptors was shown to be upregulated in NK cells in response to prolonged stimulation with recombinant interleukin 2.

Activation of D5 prevents p50, part of NF-κB protein complex, from repressing the transcription of miRNA 29a.

[43] The high degree of homology between D5 and D1 receptors and their affinity for drugs with similar pharmacological profile complicate distinguishing between them in research.

[35] A method involving mRNA probes for in situ hybridization has been developed, which allowed to separately examine the expression of D1 and D5 receptors in the mouse brain.

[20] This article incorporates text from the United States National Library of Medicine, which is in the public domain.