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

Abstract The serotonin 1B receptor knockout (5-HT 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 1 and D 2 receptor as well DA plasma membrane transporter (DAT) sites by ligand binding autoradiography, and G-protein coupling to D 1 and D 2 receptors by [ 35 S]GTPγS autoradiography. Except for a slight increase in the lateral septum, D 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 1 agonist-stimulated G-protein coupling in any of these regions, including the lateral septum. Increases in D 2 binding sites, presumably involving GABAergic projection neurons, were measured in the nucleus accumbens, olfactory tubercle and ventral tegmental area of the 5-HT 1B KO. However, no activation of the efficacy of D 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 μ-opioid and GABA B receptors was also assessed by [ 35 S]GTPγS autoradiography. 5-HT 1B KO showed selective decreases in G-protein coupling to μ-opioid receptors in the paraventricular thalamic nucleus, and to GABA 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 1B KO mouse.