Full-length cDNA cloning and distribution of human dopamine D4 receptor

Antidepressant-Like Effect of D2/3 Receptor-, but not D4 Receptor-Activation in the Rat Forced Swim Test

“…Similar to D 3 receptors, D 4 receptors have been extensively investigated as a target for the treatment of schizophrenia. Interestingly, distribution of D 4 receptors in brain areas associated with regulation of emotions and cognition such as prefrontal cortex and mesolimbic areas (Matsumoto et al, 1995;Ariano et al, 1997;Tarazi et al, 1997;Oak et al, 2000) also make them an intriguing candidate to play a role in depressive-like behaviors. However, using selective (Moreland et al, 2004), and the lack of efficacy blocking the effect of quinpirole in FST suggest that D 4 receptors are clearly not involved in the mediation of antidepressant-like activity.…”

Dopamine D4 Receptor Gene Novelty or Nonsense?

“…The levels of D4 mRNA are undetectable in the striatum using in situ hybridization, but D4-like transcripts have been detected in the prefrontal cortex and primary visual cortex (Meador-Woodruff et al 1997). Uncertainty about the role of D4 arises from the demonstration of much higher levels of D4 mRNA in the rat heart as compared to rat brain tissue (O'Malley et al 1992), although D4 has not been demonstrated in the human heart (Matsumoto et al 1995). The retina has the highest levels of D4 mRNA in humans (Matsumoto et al 1995).…”

“…Uncertainty about the role of D4 arises from the demonstration of much higher levels of D4 mRNA in the rat heart as compared to rat brain tissue (O'Malley et al 1992), although D4 has not been demonstrated in the human heart (Matsumoto et al 1995). The retina has the highest levels of D4 mRNA in humans (Matsumoto et al 1995).…”

Dopamine receptor 4 promoter polymorphism modulates memory and neuronal responses to salience

“…These findings, combined with the observations of high levels of DRD4 expression in PFC (Ariano et al, 1997;Defagot et al, 1997;Matsumoto et al, 1995) raise a possibility of C allele dose-dependent PFC responses during perceptual novelty encoding. Contrary to prediction, this genotype-dependent effect was not observed, nor do we observe adaptation of prefrontal responses with repeated oddball presentation, which has been described previously (Yamaguchi et al, 2004).…”

“…Drd4 gene knockout mice show decreased exploration in response to novel stimuli (Dulawa et al, 1999;Rubinstein et al, 1997), whereas a selective D4 receptor agonist increases novel object exploration in mice (Powell et al, 2003). The D4 receptor is preferentially expressed in limbic regions, including the hippocampus (Mrzljak et al, 1996), prefrontal cortex (Ariano et al, 1997;Defagot et al, 1997;Matsumoto et al, 1995), and globus pallidus (Mrzljak et al, 1996). Although D4 receptor expression has been shown in primate SN, this is in SN pars reticulata (Mrzljak et al, 1996) and not the SN pars compacta or VTA which contain the majority of dopaminergic neurones in the SN/VTA (Duzel et al, 2009).…”