Overview of D4 receptors

The D4 receptor, cloned by Van Tol et al. in 1991, exhibits a homology of 41% and 39% with the D2 and D3 receptors, respectively. The principal transduction mechanism of the D4 receptor is the inhibition of adenylyl cyclase the D4 receptor, however, also stimulates Na+/H+ exchange and potentiates stimulated arachidonic acid release (Chio et al., 1994 McHale et al., 1994). 

Little is known about the physiological role of the D4 receptor, except for some reports on D4 receptor role in behavioral sensitization (Feldpausch et al., 1998) and on reversal of 

Similarly to the D3 and D1B/5 receptors, the localization of the D4 receptor in the central nervous system was mostly evaluated through the localization of its mRNA and through studies using specific antibodies. The level of D4 receptor expression in the CNS was found, in general, to be lower than that of the D2 receptor. D4 receptor expression was found to be higher in limbic and cortical areas than in motor areas, suggesting a preferential involvement of these receptors in affective behavior and cognition (Civelli, 2003). 

High D4 receptor concentration has been described in the rat frontal and parietal cortex on the other hand, medium-high concentration of D4 receptor has been reported in the NAc, CPu, SNc, as well as in the hippocampus, entorhinal cortex, and medium-low concentration in the olfactory tubercle, GP, thalamus, supraoptic nucleus of the hypothalamus, cerebellum, and pituitary gland (Ariano et al., 1997b Defagot et al., 1997 Mauger et al., 1998). 

In the rodent brain, D4 mRNA has a relatively restricted pattern of expression, being localized in the frontal cortex, in the olfactory bulb, hypothalamus and thalamus in the retina, D4 mRNA is expressed in the photoreceptor cell layer and in the inner nuclear and ganglion cell layers (Cohen et al., 1992 O Malley et al., 1992). 

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