Regionally selective changes in neurotransmitter receptors in the brain of the 5-HT sub(1B) knockout mouse

The serotonin sub(1B) receptor knockout (5-HT sub(1B) 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 D sub(1) and D sub(2) receptor as well da plasma membrane transporter (DAT) sites by ligand binding autoradiography, and G-protein coupling to D sub(1) and D sub(2) receptors by [ super(35)S]GTP gamma S autoradiography. Except for a slight increase in the lateral septum, D sub(1) 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 D sub(1) agonist-stimulated G-protein coupling in any of these regions, including the lateral septum. Increases in D sub(2) binding sites, presumably involving GABAergic projection neurons, were measured in the nucleus accumbens, olfactory tubercle and ventral tegmental area of the 5-HT sub(1B) KO. However, no activation of the efficacy of D sub(2) 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 GABA sub(B) receptors was also assessed by [ super(35)S]GTP gamma S autoradiography. 5-HT sub(1B) KO showed selective decreases in G-protein coupling to mu -opioid receptors in the paraventricular thalamic nucleus, and to GABA sub(B) receptors in the basolateral nucleus of amygdala. It is likely that these latter changes underlie some aspects of the addictive behavior of the 5-HT sub(1B) KO mouse.