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Publication : Regionally selective changes in neurotransmitter receptors in the brain of the 5-HT1B knockout mouse.

First Author  Ase AR Year  2008
Journal  J Chem Neuroanat Volume  35
Issue  4 Pages  356-63
PubMed ID  18406571 Mgi Jnum  J:141712
Mgi Id  MGI:3819304 Doi  10.1016/j.jchemneu.2008.02.007
Citation  Ase AR, et al. (2008) Regionally selective changes in neurotransmitter receptors in the brain of the 5-HT1B knockout mouse. J Chem Neuroanat 35(4):356-63
abstractText  The serotonin1B receptor knockout (5-HT1B KO) mouse is a valuable animal model of addiction to psychostimulants. We previously found selective increases in dopamine (DA) turnover in the nucleus accumbens of these mice, in addition to several changes in their central serotonin system. Here, we searched for further DA adaptations by measuring D1 and D2 receptor as well DA plasma membrane transporter (DAT) sites by ligand binding autoradiography, and G-protein coupling to D1 and D2 receptors by [35S]GTP gamma S autoradiography. Except for a slight increase in the lateral septum, D1 receptor binding did not differ from wild-type in twenty-one other neocortical, limbic or basal ganglia regions examined in the KO. Nor were there changes in D1 agonist-stimulated G-protein coupling in any of these regions, including the lateral septum. Increases in D2 binding sites, presumably involving GABAergic projection neurons, were measured in the nucleus accumbens, olfactory tubercle and ventral tegmental area of the 5-HT1B KO. However, no activation of the efficacy of D2 receptor coupling to G-protein could be measured in these and other brain regions. Binding to DAT was unchanged throughout brain. Because of their implication in cocaine addiction, the functionality of mu-opioid and GABAB receptors was also assessed by [35S]GTP gamma S autoradiography. 5-HT1B KO showed selective decreases in G-protein coupling to mu-opioid receptors in the paraventricular thalamic nucleus, and to GABAB receptors in the basolateral nucleus of amygdala. It is likely that these latter changes underlie some aspects of the addictive behavior of the 5-HT1B KO mouse.
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