Therefore, somatodendritic and nerve terminal
autoreceptors act synergistically to reduce dopaminergic transmission,
and both are more sensitive to agonists than are postsynaptic dopamine
receptors. Stimulation of D2 autoreceptors reduces AC
activity, calcium influx, and neuronal excitability and promotes
membrane hyperpolarization and potassium efflux.Functions of
autoreceptors include inhibition of dopaminergic neuronal firing,
inhibition of dopamine synthesis, promotion of dopamine uptake by DAT
located on neuronal membranes and cytosolic vesicles, and enhanced DAT
expression.
Five dopamine receptor subtypes (DjR through D5R) are expressed in the brain. They have been categorized into 2 groups, Dj-like (DjR and D5R) and D2-like (D2R, D3R, and D4R), which have different mechanisms of action. Like A2AAR, D1R stimulates AC via coupled Golf protein and thereby increases production of cytosolic cyclic AMP. In contrast, D2R is coupled to Gi proteins and reduces cAMP production via inhibition of AC. DjR and D2R respectively are expressed on MSN of direct and indirect pathways (see Amaryl for diabetes), where they exert opposing effects on the activity of thalamocortical neurons. D1R stimulation promotes, whereas D2R stimulation suppresses, the activities of direct and indirect pathways. However, the output of these 2 receptors converges to jointly promote behavioral activation, and endogenous dopamine regulates MSN excitability by acting on either D1R or D2R (or both). Agonists of D1R and D2R both promote locomotion, and simultaneous administration of specific agonists of the 2 receptors results in synergistic psychomotor stimulation. In general, the pharmacologic effects of psychostimulant drugs like caffeine are mediated directly or indirectly through modulation of dopaminergic neurotransmission.
Five dopamine receptor subtypes (DjR through D5R) are expressed in the brain. They have been categorized into 2 groups, Dj-like (DjR and D5R) and D2-like (D2R, D3R, and D4R), which have different mechanisms of action. Like A2AAR, D1R stimulates AC via coupled Golf protein and thereby increases production of cytosolic cyclic AMP. In contrast, D2R is coupled to Gi proteins and reduces cAMP production via inhibition of AC. DjR and D2R respectively are expressed on MSN of direct and indirect pathways (see Amaryl for diabetes), where they exert opposing effects on the activity of thalamocortical neurons. D1R stimulation promotes, whereas D2R stimulation suppresses, the activities of direct and indirect pathways. However, the output of these 2 receptors converges to jointly promote behavioral activation, and endogenous dopamine regulates MSN excitability by acting on either D1R or D2R (or both). Agonists of D1R and D2R both promote locomotion, and simultaneous administration of specific agonists of the 2 receptors results in synergistic psychomotor stimulation. In general, the pharmacologic effects of psychostimulant drugs like caffeine are mediated directly or indirectly through modulation of dopaminergic neurotransmission.
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