| First Author | Urs NM | Year | 2014 |
| Journal | Int J Obes Suppl | Volume | 4 |
| Issue | Suppl 1 | Pages | S5-8 |
| PubMed ID | 27152166 | Mgi Jnum | J:248604 |
| Mgi Id | MGI:6094045 | Doi | 10.1038/ijosup.2014.3 |
| Citation | Urs NM, et al. (2014) The physiological relevance of functional selectivity in dopamine signalling. Int J Obes Suppl 4(Suppl 1):S5-8 |
| abstractText | We sought to determine the role of functionally selective dopamine (DA) signalling pathways (G protein or beta-arrestin) in DA-dependent behaviours. Mice that were globally deficient for beta-arrestins or mice deficient in GSK3beta in D2 receptor (D2R)-expressing neurons were used to investigate the role of functional selectivity in DA-dependent behaviours such as locomotor activity and conditioned place preference (CPP). Wild-type or knockout mice were injected with drugs such as morphine and amphetamine, which are known to increase DA levels in the brain and to induce a hyper-locomotor response and CPP. Unlike beta-arrestin1 (betaarr1)-deficient mice, mice globally deficient for beta-arrestin2 (betaarr2) mount a reduced hyperlocomotor response to either morphine or amphetamine. However, mice deficient in GSK3beta in D2R-expressing neurons show a significantly reduced locomotor response to only amphetamine but not morphine. Interestingly, all mice tested show a normal CPP response to either morphine or amphetamine. beta-arrestin-mediated DA receptor signalling has an important role in the locomotor response, but not CPP, to drugs such as morphine and amphetamine, demonstrating a functional selectivity of DA-dependent behaviours in mice. It is likely that G-protein-dependent signalling through DA receptors mediates the CPP response. |
