Role of serotonin and dopamine receptor binding in antipsychotic efficacy.

In an effort to analyse the contribution of individual serotonin and dopamine receptor subtypes to antipsychotic medication response, we analysed the correlation between clinically effective antipsychotic drug dose and binding affinity to cloned serotonin and dopamine receptor subtypes. Clinically effective dosage and binding affinity to the D(2) dopamine receptor subtype were moderately correlated for typical antipsychotic medications (r=0.57, p=0.

The dopamine D3 receptor antagonist NGB 2904 increases spontaneous and amphetamine-stimulated locomotion.

The dopamine D3 receptor is believed to play an important role in regulation of rodent locomotor behavior, and has been proposed as a therapeutic target for substance abuse, psychotic disorders, and Parkinson's disease. One model of dopamine D3 receptor function, based on studies utilizing D3 receptor knockout mice and D3 receptor-preferring agonists, proposes that D3 receptor stimulation is inhibitory to psychostimulant-induced locomotion, in opposition to the effects of concurrent dopamine D1 and D2 receptor stimulation. Recent progress in medicinal chemistry has led to the development of highly-selective dopamine D3 receptor antagonists.

Dopamine and serotonin receptor binding and antipsychotic efficacy.

The relationship between clinically effective antipsychotic drug dosage and binding affinity to cloned dopamine (DA) and serotonin receptor subtypes was analyzed in an effort to elucidate the contribution of individual receptor subtypes to medication response. Clinically effective dose and binding affinity to D(2) DA receptor were modestly correlated for typical antipsychotic medications (r=0.54, p=0.

Relative expression of D3 dopamine receptor and alternative splice variant D3nf mRNA in high and low responders to novelty.

Studies in rodents suggest an important role for the D3 dopamine receptor in regulating locomotor responses to spatial novelty and psychostimulants. The D3 receptor alternatively spliced variant D3nf produces a non-dopamine binding protein that may alter D3 receptor localization by dimerizing with the full-length receptor. In the high responder/low responder (HR/LR) model, the locomotor response to an inescapable, novel spatial environment predicts individual differences in the locomotor and rewarding effects of psychostimulants.

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

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 wild-type controls to investigate the role of the D3R in locomotor activity and stereotypy stimulated by acute amphetamine (AMPH) (0.2, 2.

Risperidone pretreatment prevents elevated locomotor activity following neonatal hippocampal lesions.

Long-standing behavioral abnormalities emerge after puberty in rats following neonatal hippocampal lesion, providing a developmental model of abnormal rat behavior that may have predictive validity in identifying compounds effective in treating symptoms of schizophrenia. We sought to test the predictive validity of the neonatal hippocampal lesion model in identifying preventive treatment for first-episode psychosis. We determined the effect of risperidone, recently studied for prevention of first-episode psychosis, on the development of elevated locomotor activity following neonatal hippocampal lesions.

Altered behavioral response to dopamine D3 receptor agonists 7-OH-DPAT and PD 128907 following repetitive amphetamine administration.

Behavioral sensitization, the progressive and enduring enhancement of certain behaviors following repetitive drug use, is mediated in part by dopaminergic pathways. Increased locomotor response to drug treatment, a sensitizable behavior, is modulated by an opposing balance of dopamine receptor subtypes, with D1/D2 dopamine receptor stimulation increasing and D3 dopamine receptor activation inhibiting amphetamine-induced locomotion. We hypothesize that tolerance of D3 receptor locomotor inhibition contributes to behavioral sensitization.

7-OH-DPAT and PD 128907 selectively activate the D3 dopamine receptor in a novel environment.

The D3 dopamine receptor is expressed primarily in limbic brain areas, and appears to play an inhibitory role in rodent locomotor behavior. Evidence suggests a potential role for the D3 receptor in the pathology of neuropsychiatric disease. Progress in elucidating D3 receptor function has been hampered, however, by a lack of well-characterized, selective ligands and by conflicting information regarding the behavioral phenotype of D3 receptor knockout mice.