Prodynorphin-derived peptide expression in primate cortex and striatum

The distributions of four prodynorphin-derived peptides, dynorphin A (1-17), dynorphin A (1-8), dynorphin B, and [alpha]-neo-endorphin were determined in 10 cortical regions and the striatum of the old world monkey (Macaca nemestrina). [alpha]-neo-endorphin was the most abundant peptide in both cortex and striatum. The concentrations of all four peptides were significantly greater in the striatum compared to the cortex. In general, concentrations of each peptide tended to be higher in allocortex than in neocortex. Possible inter- and intradomain processing differences, as estimated by ratios of these peptides, did not vary within cortex, but the intradomain peptide ratio, dyn A (1-17)/dyn A (1-8), was significantly greater in cortex than in striatum. These results indicate that prodynorphin is, in some ways, uniquely processed in the primate. Particularly unusual is the relatively low abundance of prodynorphin-derived products in the cortex, in the face of moderately high levels of kappa opiate receptor expression.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31211/1/0000113.pd

Severity of depression and hypothalamic-pituitary-adrenal axis dysregulation: identification of contributing factors

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65507/1/j.1600-0447.1990.tb05465.x.pd

Dopamine receptor messenger RNA: Localization in the human hippocampus

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30871/1/0000535.pd

Distribution of D2 dopamine receptor mRNA in the primate brain

1. The distribution of the messenger RNA (mRNA) encoding the D2dopamine receptor has been mapped in the monkey brain by hybridization.2. Using [35s]-labelled riboprobes corresponding to the region of the D2 dopamine receptor spanning the third cytosolic loop and the sixth and seventh transmembrane domains, specific hybridization was observed in a number of neural structures.3. High levels of mRNA expression were observed in the caudate, putamen, and claustrum. Significant amounts were also identified in the hippocampus, lateral geniculate nucleus, much of the cortex, amygdala, pons, and thalamus. High levels of this mRNA were also visualized in the substantia nigra, likely reflecting autoreceptor synthesis.4. While the distribution of D2 dopamine receptor mRNA was similar between the monkey and previously published maps in the rat, several differences were noted.5. These results demonstrate the feasibility of visualizing this mRNA in the primate brain, and suggest that a similar analysis of human postmortem brain material may be possible.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29649/1/0000738.pd

Plasma postdexamethasone cortisol levels in schizoaffective disorder

The degree of hypothalamic-pituitary-adrenal (HPA) axis dysregulation in depressed patients with schizoaffective disorder was compared to that seen in patients with major depressive disorder with and without delusional features. The frequency of nonsuppression to dexamethasone was similar for all three diagnostic groups. Maximum postdexamethasone plasma cortisol was greater for delusional depressives, but did not differ between patients with major depressive and schizoaffective disorders. Modest correlations were found between postdexamethasone plasma cortisol levels, severity of illness, age, and recent weight loss, for patients with both major depressive disorder and delusional depression. For schizoaffective patients, associations between postdexamethasone plasma cortisol levels and various measures of severity of illness, but not age and recent weight loss, were found. Although HPA axis dysregulation occurs more frequently in all three of the studied diagnostic groups than in normal individuals, factors contributing to this dysregulation may be qualitatively different for schizoaffective patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27102/1/0000094.pd

Dexamethasone suppression test status and severity of depression

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27129/1/0000122.pd

A comparison of D1 receptor binding and mRNA in rat brain using receptor autoradiographic and in situ hybridization techniques

D1, a subtype of the dopamine receptors, is widely distributed in the nervous system and has been shown to be positively coupled to adenylate cyclase. Using a combination of in vitro receptor autoradiographic and in situ hybridization techniques, the present study examines the co-distribution of D1 receptor binding sites and D1 receptor messenger RNA in adjacent rat brain sections. D1 receptor binding sites were labeled using the selective antagonist [3H]SCH23390 (4.6 nM) in the presence of 1 [mu]M ketanserin, while the D1 receptor messenger RNA was visualized with a 35S-labeled riboprobe corresponding to a region between transmembrane domains III and VI of the rat D1 receptor (bp 383-843). Analysis of serial sections suggested a good agreement between D1 receptor binding and messenger RNA in several brain regions, including the paleocortex, caudate-putamen, nucleus accumbens, amygdala and suprachiasmatic nucleus. Marked discrepancies between D1 receptor binding and messenger RNA were observed in other brain regions including the entopeduncular and subthalamic nuclei, substantia nigra (pars reticulata), hippocampus and cerebellum. While technical considerations may contribute to these results, much of the discordance between the distributions is likely due to the differential localization D1 receptor messenger RNA in cell bodies and receptor binding sites on fibers and may provide insights into receptor synthesis, transport and membrane insertion. In the basal ganglia, for instance, D1 receptors are synthesized in the striatum and are either transported to efferent projections in areas such as the substantia nigra, or remain localized in striatal cells bodies. Ibotenic acid lesions in the striatum are consistent with these conclusions and demonstrate a coordinate loss of D1 receptor binding and messenger RNA in the caudate-putamen that is accompanied by a degeneration of fibers projecting to substantia nigra and a loss of D1 binding in the pars reticulata. Neurons in the dentate gyrus and in the granular layer of the cerebellum, on the other hand, synthesize D1 receptors and transport them entirely to either their dendritic or axonal fields, respectively, in the molecular layer.This analysis provides a better understanding of dopaminergic receptor systems in the CNS and their anatomical organization.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29608/1/0000697.pd

Postdexamethasone plasma cortisol and [beta]-endorphin levels in depression: Relationship to severity of illness

The hypothalamic-pituitary-adrenal (HPA) axis is dysregulated in many patients with depression, probably at all levels of the axis. To determine if HPA dysregulation is associated with severity of depression, we studied a group of 66 patients with major depressive disorder. Each patient underwent a pretreatment Dexamethasone Suppression Test, with plasma postdexamethasone cortisol determination at 8:00 AM, 4:00 PM, and 11:00 PM. All three postdexamethasone cortisol levels were significantly correlated with the Hamilton Rating Scale for Depression (HRSD) scores. We also examined the "profile" measures of mean, maximum, and minimum of the three cortisol values; again, all three were significantly correlated with HRSD scores. To evaluate associations between clinical severity and HPA dysregulation at the pituitary level, we studied a second group of 44 patients with major depressive disorder. Each had postdexamethasone cortisol determinations at 4:00 PM and 11:00 PM as well as pre- and postdexamethasone [beta]-endorphin determinations at 4:00 PM. The cortisol data from this group followed the same pattern as in the first sample, and there was a significant relationship between HRSD score and degree of [beta]-endorphin nonsuppression as well. These results suggest that severity of depression is one of the determinants of dysregulation at both adrenal and pituitary levels of the HPA axis, accounting for 10%-20% of the observed variance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26603/1/0000144.pd

Distribution of D5 dopamine receptor mRNA in rat brain

The distribution of the messenger RNA encoding the dopamine D5 receptor was determined in the rat brain by in situ hybridization. Using [35S]-labelled riboprobes to either the rat or human D5 receptor, this mRNA was localized to the hippocampus and the parafascicular nucleus of the thalamus. This mRNA could not be visualized in the more traditional brain regions associated with dopaminergic cell bodies or projection fields. This unusual distribution suggests a novel function in the brain for this subtype of the dopamine receptor.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29790/1/0000132.pd

Multiple depressive episodes and plasma postdexamethasone cortisol levels

The hypothalamic-pituitary-adrenal (HPA) axis is dysregulated in many patients with major depressive disorder (MDD). To determine whether or not a past history of depressive episodes is associated with this dysregulation, we studied the relationships among number of past depressive episodes, number of previous hospitalizations for depression, and number of years since first depressive episode and biological markers of depression (postdexamethasone plasma cortisol levels and dexamethasone suppressor/nonsuppressor status). No significant relationships were detected.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26723/1/0000273.pd