Dose–response analysis of locomotor activity and stereotypy in dopamine D3 receptor mutant mice following acute amphetamine

Abstract

Accumulating evidence suggests that dopamine D3 receptor (D3R) stimulation is inhibitory to spontaneous and psychostimulant-induced locomotion through opposition of concurrent D1R and D2R-mediated signaling. To evaluate this model, we used homozygous D3R mutant mice and wildtype controls to investigate the role of the D3R in locomotor activity and stereotypy stimulated by acute amphetamine (AMPH) (0.2, 2.5, 5.0, 10.0 mg/kg). At the lowest dose tested (0.2 mg/kg), neither D3R mutant mice nor wild-type mice exhibited measurable change in locomotor activity or stereotypy relative to their respective saline-treated controls. D3R mutant mice exhibited a significantly greater increase in locomotor activity, but not stereotypy, relative to wild-type mice in response to treatment with AMPH 2.5 mg/kg. AMPH-induced locomotor activity and stereotypy were similar in both wild-type and D3R mutant mice at both the 5.0 and 10 mg/kg AMPH doses. These findings provide further support for an inhibitory role for the D3R in AMPH-induced locomotor activity, and demonstrate a more limited role for the D3R in modulating AMPH-induced stereotypy.

D2 dopamine receptor subtype-mediated hyperactivity and amphetamine responses in a model of ADHD

“…In control mice, the response to amphetamine was apparently unaffected by the D3 dopamine receptor deletion (Fig. 1b), although there was an overall trend for an increase in locomotor activity in D3 dopamine receptor null mice (+/+;D3 -/- ) when the data were collapsed over treatment (p <0.05), consistent with a previous report (McNamara et al, 2006). …”

“…There was an overall increase in locomotor activity of D3 dopamine receptor null mutants consistent with previous reports (Accili et al, 1996; McNamara et al, 2006; Xu et al, 1997). However, the D3 dopamine receptor antagonist S33084 had little effect on baseline and amphetamine-stimulated locomotor activity in normal mice.…”

“…D3 dopamine receptors are thought to damp or inhibit spontaneous and psychostimulant-mediated locomotor activity (De Boer et al, 1997; McNamara et al, 2006; Ouagazzal and Creese, 2000), suggesting a role for these receptors in hyperactivity. There was an overall increase in locomotor activity of D3 dopamine receptor null mutants consistent with previous reports (Accili et al, 1996; McNamara et al, 2006; Xu et al, 1997).…”

Effects of Pro-Gly-Pro Tripeptide on the Dopamine System

“…It is assumed that psychomimetics stimulate motor and stereotypical activities of experimental animals through postsynaptic D 1 and D 2 dopamine receptors, while D 3 receptor stimulation inhibits locomotion [12,13]. On the other hand, it was shown that the yawning phenomenon is primarily caused by stimulation of presynaptic D 3 receptors, while D 2 autorecep- tors mediate its inhibition [11].…”

Dopamine D4 receptor deficiency in mice alters behavioral responses to anxiogenic stimuli and the psychostimulant methylphenidate

“…Additionally, the computer allowed us to define a square center region (20 cm× 20 cm, edges 10 cm from each wall) and the total time spent in this region was quantified during each test stage. Besides the automated measures of motor activity, we quantified behavioral intensity in response to MP treatment using a rating scale adapted from McNamara et al (2006). Mouse behavior was scored from video recordings by a trained observer, blind to genotype and treatment condition, in 10 30-second intervals, starting at three and a half minutes and occurring every 4 minutes for 40 minutes (the length of the assay).…”