Carmencita Pilapil

Plasma melatonin—An index of brain aging in humans?

We investigated the age-related changes in the circadian rhythm of plasma melatonin as a potential index of brain aging in man. The subjects were 5 young men aged 19-25 years, 11 older men aged 51-65 years, 6 elderly men aged 66-89 years, 7 young women aged 19-25 years, 5 premenopausal women aged 45-50 years, 8 postmenopausal women aged 51-65 years, and 5 elderly women aged 66-75 years. They were all physically and psychiatrically normal. Serial blood samples were drawn from 8:00 AM until 8:00 AM on the next day, with the indoor illumination set at 300 Lux from 7:00 AM until 4:00 PM and at 50 Lux thereafter. Plasma melatonin was estimated by radioimmunoassay. The results show that there is a significant negative correlation between age and 24-hr secretion of plasma melatonin (r = -0.952, p less than 0.0001), between age and peak levels of plasma melatonin (r = -0.937, p less than 0.00001), and between age and the lag in time from sunset to the onset of significant elevation of plasma melatonin over daytime values (r = 0.916, p less than 0.0001). It is concluded that study of the circadian rhythm of plasma melatonin may prove to be a useful index of the aging process.

Circadian rhythm of plasma melatonin in endogenous depression

The circadian rhythm of plasma melatonin was investigated in normal men 18-30 years (N = 5), normal men 50-70 years (N = 5) and in six patients with endogenous depression. The environmental photoperiod was 11 hours. The subjects and patients were indoors with lights on from 07:00 until 23:00 hours. Blood samples were obtained every 4 hours over a 24 hour period, with additional sampling at 22:00 and 02:00 hours. Plasma melatonin was estimated by radioimmunoassay compared to both groups of controls. In the depressed patients, the levels of melatonin were low throughout the 24 hour period. The depressives had a delayed onset of the dark phase of the rhythm. The patients also showed peak melatonin levels occurring earlier than in the controls. Circadian rhythm of melatonin and therefore of its pacemaker may be altered in endogenous depression.

Autoradiographic distribution of multiple classes of opioid receptor binding sites in human forebrain

Receptor binding parameters and autoradiographic distribution of various opioid receptor sites have been investigated in normal human brain, post-mortem. [3H]DAGO, a highly selective mu ligand, binds to a single class of high affinity (Kd = 1.1 nM), low capacity (Bmax = 160 fmol/mg protein) sites in membrane preparations of frontal cortex. These sites show a ligand selectivity profile that resembles that of the mu opioid receptor. On the other hand, [3H]bremazocine, in presence of saturating concentrations of mu and delta blockers, appears to selectively bind to a single population of kappa opioid sites (Kd = 0.13 nM; Bmax = 93.0 fmol/mg protein) in human frontal cortex. Whole hemisphere in vitro receptor autoradiography reveals that [3H]DAGO-mu, [3H]DSLET-delta and [3H]bremazocine (plus blockers)-kappa binding sites are discretely and differentially distributed in human forebrain. In the cortex, mu sites are concentrated in laminae I and IV, delta sites in laminae I and II while kappa sites are found in deeper layers (laminae V and VI). In subcortical nuclei, high densities of mu and delta sites are seen in the caudate and putamen while high amounts of kappa sites are present in the claustrum and amygdala. The nucleus basalis of Meynert is enriched in all three classes of sites while the globus pallidus only contains moderate densities of kappa sites. Thus, the possible alterations of these various classes of opioid receptors in neurological and psychiatric diseases certainly deserve further investigation.

Comparative potencies of substance P, substance K and neuromedin K on brain substance P receptors.

The relative potency of substance P, substance K and neuromedin K on [3H]substance P binding has been compared in rat brain membrane preparations. Substance K and neuromedin K, two newly isolated substance P-related mammalian peptides, are very weak competitors for [3H]substance P binding sites. It suggests that these two neuropeptides are not acting on the same receptor type as substance P. Moreover, previous substance P receptor classifications are unlikely to be applicable to brain tachykinin receptor sub-types.

Localization of kappa opioid receptor binding sites in human forebrain using [3H]U69,593: Comparison with [3H]bremazocine

Summary1.The autoradiographic distribution of kappa opioid receptor binding sites in human brain was examined using two radiolabeled probes, namely [3H]U69,593 and [3H]bremazocine.2.[3H]U69,593 binding was performed in the absence of blockers for other sites, while [3H]bremazocine binding was investigated in the presence of saturating concentrations of mu and delta blockers to ensure selective labeling of kappa opioid receptors.3.Our results show that the autoradiographic distribution of [3H]U69,593 and [3H]bremazocine (plus blockers) binding sites is identical, with high densities of sites found in deep cortical layers and claustrum.4.This indicates that [3H]U69,593 is a highly selective ligand of the kappa opioid receptor type.

Autoradiographic distribution of [3H]dexoxadrol (a phencyclidine-related ligand) binding sites in rat and human brain

[3H]dexoxadrol, a dissociative anesthetic, binds with high affinity to specific sites in rat brain (membrane binding and light microscopic autoradiography). Various phencyclidine (PCP) analogues compete for [3H]dexoxadrol sites in a slightly different manner than against [3H]PCP binding sites. As for [3H]PCP binding, [3H]dexoxadrol binding sites are highly concentrated in brain regions such as the cortex and the hippocampus. However, other areas such as the hypothalamus are enriched only in [3H]dexoxadrol binding sites. This suggests that [3H]dexoxadrol binds to PCP-related sites in certain brain regions but not in others. In the human forebrain, [3H]dexoxadrol binding sites are distributed as in the rat brain and mainly found in the caudate, putamen and cortex.

Effect of Imipramine on the Circadian Rhythm of Plasma Melatonin in Unipolar Depression

The authors took a series of 20 serum samples over a 24-hr period for measurement of melatonin in four men and six women with Major Depressive Disorder (DSM-III), at baseline (depressed) and after 4 weeks on imipramine (150-200 mg/day) after achieving clinical remission. After successful treatment with imipramine, 24-hr secretion and peak levels of melatonin were significantly higher than at baseline, with no difference in time of peak level. Testing after 2 weeks of treatment (four subjects), with only a partial or no clinical response, revealed no differences compared with baseline. The therapeutic efficacy of imipramine may be associated with an enhancement of noradrenergic activity.

Effect of apomorphine on melatonin secretion in normal subjects.

There is some evidence in animals that dopamine (DA) affects melatonin secretion. The effect of apomorphine (Apo), a selective DA receptor agonist, and placebo on day-time melatonin secretion was studied in six normal men. Apo HCl in a dose (0.5 mg sc) which increased growth hormone secretion in all subjects had no effect on day-time melatonin concentrations in plasma. In keeping with other clinical studies these data suggest that melatonin secretion is not regulated by a DA mechanism in man.