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Annotation

Higley MJ, Sabatini BL. Competitive regulation of synaptic Ca2+ influx by D2 dopamine and A2A adenosine receptors. Nat Neurosci . 2010 Aug ; 13(8):958-66. PubMed Abstract

Comments on Paper and Primary News
Comment by:  Philip Seeman (Disclosure)
Submitted 12 July 2010 Posted 12 July 2010

There are multiple pathways to psychosis and schizophrenia, all associated with dopamine supersensitivity and elevated amounts of D2High receptors (Seeman et al., 2005; Seeman et al., 2006; Seeman, 2008; Seeman, 2010; Seeman, 2009). The present paper by Higley and Sabatini is consistent with the multiple-pathway hypothesis. They show that the dopamine D2 receptor, which is the main target for antipsychotic drugs (Seeman et al., 1975; Seeman et al., 1976), regulates the multiple pathways of glutamate and adenosine transmission. Their work is also consistent with the fact that a glutamate agonist can treat schizophrenia (Patil et al., 2007), especially when such a glutamate drug can stimulate glutamate receptors and partly inhibit dopamine D2High...  Read more


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Comment by:  Jose Bargas
Submitted 6 September 2010 Posted 16 September 2010
  I recommend this paper

In a recent study by Kravitz et al., 2010, it is shown, also with optogenetic techniques (channelrhodopsin expressed in direct or indirect medium spiny neurons—MSNs—of transgenic mice), that specific stimulation of D2R-expressing indirect pathway MSNs (with an implanted laser) causes akinesia and rigidity in the animals as long as the laser stimulus is on. Once the illumination is turned off, the behavior returns to normal. Moreover, they show that stimulation of D1R-expressing direct pathway MSNs cause the opposite: hyperkinesia and hyperactivity. Furthermore, if a partial parkinsonism is induced in these mice, direct pathway stimulation rescues the animals from the pathological condition. These experiments give strong support to the basal ganglia pathophysiological model launched by Albin et al. (1989) more than 20 years ago. This model is based in the following assumptions: 1) dopamine acting on D1R stimulates direct pathway MSNs firing, and that facilitates...  Read more


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