The D1-like dopamine receptors are coupled to the Gα s, which activates adenylate cyclase to produce a higher level of cyclic adenosine monophosphate (cAMP) and then enhances the activity of protein kinase A (PKA). The GPCR receptors participate in synaptic transmission in brain neural circuits by activating the G protein to induce intracellular signaling. ĭopamine receptors differ in structure and pharmacology, and they are classified into different metabotropic G protein-coupled receptors (GPCRs) subfamilies with seven transmembrane-spanning domains. It has been shown that D4 receptors mainly locate in the prefrontal cortex, hippocampus, hypothalamus, and mesencephalon. In particular, the D3 receptor can form a heteromer with the D1 or D2 receptor and express in areas associated with psychiatric disorders, such as NAc, thalamus, hippocampus. The expression of D3 receptor in the brain is much less than that of D2 receptor. As far as the D2-like receptor family is concerned, the D2 receptor is mainly located in the core of NAc, striatum, and olfactory tubercle. Both D1 and D5 receptors are expressed in pyramidal neurons of the cortex, including the prefrontal cortex and anterior cingulate cortex. In contrast, the D5 receptor is mainly expressed in the hippocampus, the lateral mammillary nucleus, and parafascicular nucleus of the thalamus. The D1 receptor mainly distributes in the striatum, nucleus accumbens (NAc), olfactory tubercle, hypothalamus, and thalamus. The dopamine receptors distribute differentially in the brain. In addition, D1 and D5 receptors share very high homology in their transmembrane domains, while D2, D3, and D4 receptors are closely related with highly conversed transmembrane sequences. The D1-like receptor family includes D1 and D5 receptors, while the D2-like receptor family includes D2, D3, and D4 receptors. These dopamine receptors have differing pharmacological, biochemical, and physiological functions. Dopamine receptors include D1-like and D2-like receptors. Most of them are involved in the ascending pathways, and a few of them are related to descending pathways. There are several dopaminergic cell groups from A8 to A16 that distribute in different areas of the brain. The ventral side of the mesencephalon contributes to 90% of the dopaminergic neurons. Most dopaminergic neuron cell groups are derived from a single embryological cell group that originates at the mesencephalic–diencephalic junction. ĭopaminergic neurons mainly originate from the midbrain, including the ventral tegmental area (VTA), substantia nigra (SN), and hypothalamus. Low frequency tonic firing in dopaminergic neurons is mainly related to the selection of habitual motor programs independent of reward, while high frequency phasic bursts of action potential in dopaminergic neurons are related to a reward seeking movement. The dopaminergic neuron firing patterns correlate with different behaviors. Dopamine is stored in the vesicles that are released into the synaptic cleft, which is controlled by phasic and tonic transmission. As a monoamine neurotransmitter, synthesis of dopamine is limited by tyrosine hydroxylase. These self-regulating mechanisms do not require conscious thought or an act of will, they just happen like a reflex.Dopamine is derived from its precursor named L-3, 4-dihydroxyphenylalanine (L-DOPA), which is converted into dopamine by aromatic amino acid decarboxylase. Hence, everytime the balance tips towards pleasure, powerful self-regulating mechanisms kick into action to bring it level again. It does not want to be tipped for very long, to one side or another. It wants to remain level! that is, in equilibrium. But here's the important thing about the balance. The more our balance tips and the faster it tips, the more pleasure we feel. When we experience pleasure, dopamine is released in our reward pathway and the balance tips to the side of pleasure. When nothing is on the balance it's level with the ground. Imagine our brains contains a balance, a scale with a fulcrum in the centre. Another way to say this is pleasure and pain work like a balance. In addition to the discovery of dopamine, neuro-scientists have determined that pleasure and pain are processed in overlapping brain regions, and work via an opponent processing mechanism.
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