raclopride and Depressive-Disorder

Several lines of evidence indicate the involvement of the dopamine system in depressive states. In this post-mortem study, the binding of [(3)H]raclopride to dopamine D(2) receptors in the caudate nucleus was investigated in 13 depressed suicide victims and 19 controls. There were no differences in B(max) or K(d) between the two groups. A subgroup consisting of individuals with major depression, however, had significantly higher K(d) values than controls. Previous findings regarding changes in dopamine metabolism in depression and antidepressant effects of dopamine agonists seem, according to the present study, not to be reflected by alterations in density or affinity of dopamine D(2) receptors in depressed suicide victims.

Topics: Adult; Aged; Aged, 80 and over; Brain Chemistry; Caudate Nucleus; Depressive Disorder; Dopamine Antagonists; Female; Humans; Kinetics; Male; Middle Aged; Raclopride; Radioligand Assay; Receptors, Dopamine D2; Suicide

To examine the relation between dopamine (DA) D2 receptor-specific binding and personality, we assessed the relation between DA D2 binding and the NEO Personality Inventory-Revised (NEO PI-R).. Previous studies have demonstrated a relation between DA D2 receptor-specific binding and a personality trait involving personal detachment as defined by the Karolinska Scales of Personality: A subsequent study using a different measure of personal detachment failed to replicate this finding, suggesting that metric properties of the personality scale may be important. To further examine this issue, we assessed the relation between DA D2 binding and a third personality measure, the NEO PI-R.. Eighteen adult subjects completed the NEO PI-R and participated in an 11C-raclopride positron emission tomography study to quantify striatal DA D2 receptor binding.. We did not find a significant relation between binding and detachment-like traits on the NEO PI-R; however, we found a significant relation between DA D2 receptor binding and the NEO PI-R personality facet of Depression (r = 0.75, p <0.0001).. The results fail to replicate the findings of previous studies reporting an association between DA D2 receptor density and personal detachment, suggesting that the relation is relatively specific to the trait defined by the Karolinska Scales of Personality. The relation between a nonclinical personality trait of depression and DA D2 binding, if replicated, may help to elucidate the role of dopamine in depression.

Topics: Adult; Brain; Depressive Disorder; Female; Humans; Male; Object Attachment; Personality Inventory; Psychometrics; Raclopride; Receptors, Dopamine D2; Reference Values; Sensitivity and Specificity; Tomography, Emission-Computed

The densities of dopamine-D4 receptors were determined in postmortem samples of caudate nucleus from patients with schizophrenia (n = 9) and age-matched controls (n = 10). D4 receptor binding was defined as the difference between binding sites labeled by [3H]YM-09151-2 (D2 + D3 + D4 receptors) and those by [3H]raclopride, in the presence of 5'-guanylylimidodiphosphate (Gpp(NH)p) (D2 + D3 receptors). D4 receptor binding was measurable in all the subjects with schizophrenia (mean = 3.8 pmol/g tissue) but only in 3/10 controls. To determine the specificity of these findings for schizophrenia, D4 receptor binding was also measured in the caudate nucleus of suicide victims with major depression (n = 6) and age-matched controls (n = 6). A small amount of D4 binding was noted in some of the controls + depressed subjects and there was no significant difference between controls and patients with major depression. The addition of 200 microM Gpp(NH)p to the assay significantly increased the amount of specific binding of [3H]raclopride in control tissues, but not in tissues from subjects with schizophrenia, suggesting an abnormality in the G-protein component coupled to the D2 receptor. [3H]Raclopride binding was also significantly increased by Gpp(NH)p in subjects with major depression. These results confirm a previous report of Seeman et al. (1993) and suggest that measurable D4 receptor binding in the caudate nucleus is more frequent in patients with schizophrenia as compared with normal controls and subjects with major depression and that guanine nucleotides do not enhance [3H]raclopride binding in schizophrenia.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Benzamides; Caudate Nucleus; Depressive Disorder; Dopamine Antagonists; Female; GTP-Binding Proteins; Guanine Nucleotides; Guanylyl Imidodiphosphate; Humans; In Vitro Techniques; Kinetics; Male; Middle Aged; Raclopride; Receptors, Dopamine; Receptors, Dopamine D2; Receptors, Dopamine D4; Salicylamides; Schizophrenia

Rats, subjected chronically (10-12 weeks) to a variety of mild, unpredictable stressors, showed a decrease in their consumption of weak sucrose solutions; normal behavior was restored by chronic (5-9 weeks) treatment with the tricyclic antidepressant imipramine. Acute administration of the dopamine receptor antagonist pimozide or the specific dopamine D2 receptor antagonist raclopride had no effect in nonstressed animals and in vehicle-treated stressed animals, but both drugs selectively reversed the improvement of performance in imipramine-treated stressed animals. The 5HT antagonist metergoline increased sucrose consumption in all groups. The data suggest that the mechanism of action of imipramine in this model is an increase in functional activity at dopamine (DA) synapses.

Topics: Animals; Appetitive Behavior; Arousal; Depressive Disorder; Drinking; Imipramine; Male; Metergoline; Pimozide; Raclopride; Rats; Rats, Inbred Strains; Receptors, Dopamine; Salicylamides; Taste