No abstract

Compelling evidence suggests that major depression is associated with dysfunction of the brain glutamatergic transmission, and that the glutamatergic N-methyl-d-aspartate (NMDA) receptor plays a role in antidepressant activity. Recent post-mortem studies demonstrate that depression is associated with altered concentrations of proteins associated with NMDA receptor signalling in the brain. The present study investigated glutamate signalling proteins in the amygdala from depressed subjects, given strong evidence for amygdala pathology in depression. Lateral amygdala samples were obtained from 13-14 pairs of age- sex-, and post-mortem-interval-matched depressed and psychiatrically healthy control subjects. Concentrations of NR1 and NR2A subunits of the NMDA receptor, as well as NMDA receptor-associated proteins such as post-synaptic density protein-95 (PSD-95) and neuronal nitric oxide synthase (nNOS) were measured by Western immunoblotting. Additionally, levels of enzymes involved in glutamate metabolism, including glutamine synthetase and glutamic acid decarboxylase (GAD-67), were measured in the same amygdala samples. NR2A protein levels were markedly and significantly elevated (+115%, p=0.03) in depressed subjects compared to controls. Interestingly, PSD-95 levels were also highly elevated (+128%, p=0.01) in the same depressed subjects relative to controls. Amounts of NR1, nNOS, glutamine synthetase, and GAD-67 were unchanged. Increased levels of NR2A and PSD-95 suggest that glutamate signalling at the NMDA receptor in the amygdala is disrupted in depression.

Summary. Sixteen

The effects of implanting Silastic capsules containing melatonin on plasma melatonin and prolactin levels were investigated in pinealectomized (Px) and sham-operated sheep (SPx). Prior to implantation, melatonin was found in plasma samples obtained during the night period from SPx sheep (mean value 150 pg/ml), but could not be (less than 25 pg/ml) detected in plasma samples obtained during the day in SPx sheep or in any sample obtained during the night or day period in Px sheep. Following implantation, a constant basal plasma melatonin level of about 165 pg/ml was established in all sheep with a superimposed nighttime rise in SPx animals suggesting no diminution of endogenous melatonin production during the dark period. Following melatonin treatment, there was a marked depression in plasma prolactin levels in both SPx and Px sheep. These results are interpreted to indicate that 1) there is no negative feedback of melatonin upon its own synthesis and release, 2) that there is no circadian change in the rate of metabolism of melatonin and 3) that constant melatonin availability in sheep caused a depression in plasma prolactin levels similar to that found following exposure of animals to a short day.