Chronic antidepressant treatment modulates the release of somatostatin in the rat nucleus accumbens (original) (raw)
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Somatostatin content and receptors in the cerebral cortex of depressed and control subjects
Journal of Neurology, Neurosurgery & Psychiatry, 1988
Somatostatin-like immunoreactivity is reduced in the cerebrospinal fluid in depression and this is presumed to reflect alterations in cerebral somatostatinergic systems. We have examined this hypothesis by measuring this immunoreactivity and somatostatin receptors in post-mortem cortical tissue from depressed patients and control subjects. There was no significant difference in the temporal and occipital cortex in somatostatin-like immunoreactivity or in somatostatin receptor affinity and binding capacity between depressed and control groups. It is concluded that there may not be an alteration of cortical somatostatin function in depression.
Low levels of somatostatin in human CSF mark depressive episodes
Psychoneuroendocrinology, 1984
Somatostatin-like immunoreactivity was measured in the cerebrospinal fluid (CSF) of 85 inpatients with current or recent episodes of major depressive disorders, diagnosed according to Research Diagnostic Criteria (RDC) as assessed with the Schedule for Affective Disorders and Schizophrenia (SADS). Several biopsychiatric tests were run during the same week of investigation. Results indicate low levels of CSF somatostatin to be a state marker for episodes of depression characterized by sad appearance, feelings of tiredness, insomnia, and subjective inability to acknowledge any external precipitants for the depression. CSF somatostatin was negatively related to platelet monoamine oxidase (MAO) activity; MAO activity appeared to account better for the degree of melancholic features than did somatostatin. The ratio between 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) in CSF also correlated negatively with somatostatin. A positive relationship was noted between CSF xanthine and somatostatin. There was a highly significant curvilinear correlation between CSF somatostatin and serum TSH concentrations, but no correlations between CSF somatostatin and serum GH or prolactin, or with plasma cortisol before or after dexamethasone. SOMATOSTATIN is a cyclic tetradecapeptide (MW 1640 daltons) that inhibits the release of growth hormone (GH) from the pituitary (Vale et al., 1975). The name "panhibin" has been suggested to emphasize its powerful inhibitory function in a number of systems, including TSH release (McCann, 1982). Somatostatin-like immunoreactivity is widely distributed in rat brain (Brownstein et al., 1975; Kobayashi et al., 1977). In a post-mortem study on humans, Eckernas et al. (1978) found rather high concentrations of somatostatin in the neostriatum, while the highest levels were localized in the hypothalamus and in the medial part of the amygdaloid complex. S¢rensen (1982) studied human brain material obtained during neurosurgical operations of twelve patients and found somatostatinpositive cell bodies to be widely distributed and present in all cortical layers and in all areas studied (frontal, parietal and temporal). Cell bodies were numerous in the cortex, especially in layer I, where somatostatin fibers were in close contact with other cells. Very large somatostatin cells with long fibers were found throughout the subcortical white matter. Somatostatin-and avian pancreatic polypeptide (APP)-like immunoreactivities were reported by Vincent et al. (1982) to coexist in the rat forebrain (neocortex, hippocampus, and other areas) and, at least in the peripheral nervous system, somatostatin has been shown to occur in some sympathetic noradrenergic neurons (HOkfelt et al., 1977). The importance of the somatostatin system is demonstrated by the finding of this peptide in all regions of the fetal rat brain as early as 14 days post-mating (McGregor et al., 1982).
Effects of acute and chronic desipramine treatment on somatostatin receptors in brain
Psychopharmacology, 1992
The effects of acute (5 mg/kg, IP twice daily for 2 days) and chronic (5 mg/kg IP twice daily for 21 days) administration of desipramine (DMI) on [~25I]-Tyr ~ X-somatostatin binding sites in brain were examined. There was no change in [125i]Tyrl 1-somatostatin binding in membranes prepared from the frontal cortex, striatum, and hippocampus of rats acutely or chronically treated with DMI as compared to non treated animals. [125I]Tyrll-Somatostatin binding was increased in membranes prepared from the rat nucleus accumbens only after chronic DMI administration. Scatchard analysis of the binding data from the nucleus accumbens showed that [125I]Tyrll-somatostatin labels a single population of somatostatin binding sites with an affinity constant, Kd, of 1.8 + 0.60 nM and a Bm,~ of 330+ 90 fmol/mg protein. Chronic treatment with DMI increased the Bin, x (500 i 140 fmol/mg protein) but had no effect on the Kd. This finding shows a regional effect of DMI on [125I]Tyrl~-somatostatin binding sites in rat brain and suggests that somatostatin may play a role in the pathophysiology of depression.
Pharmacological Reports, 2013
Neuropeptides have been implicated in the physiology and pathophysiology of stress responses and therefore may play an important role in the pathogenesis of affective disorders such as Major Depression Disorder (MDD). The data presented in this mini-review demonstrate the role of prolactin (PRL) and somatostatin (STT) in the pathology and pharmacotherapy of MDD, focusing particularly on the response to antidepressant treatment, and compare the available data with the results obtained in our laboratory using the well-validated chronic mild stress (CMS) animal model of MDD. Despite the availability of many pharmacological therapies for depression, ca. 35% patients remain treatment resistant. This clinical situation is also true for rats subjected to CMS; some animals do not respond to antidepressant therapy and are considered treatment resistant. The most interesting results presented in this mini-review concern the changes in PRL and SST receptors in the brains of rats subjected to the full CMS procedure and IMI treatment and demonstrate the role of these receptors in the mechanisms of antidepressant action. The possible interaction between SST and PRL, the involvement of the D 2 dopamine receptor, and their direct protein-protein interactions are also discussed, with the conclusion that these two neurohormones play an important role in the mechanism of resilience after stress as well as in the mechanism of action of antidepressant drugs.
European Journal of Neuroscience, 2001
Dopamine and somatostatin have been implicated in the pathophysiology of depression. We have employed in vivo microdialysis to investigate the regulation of dopamine release by somatostatin in the nucleus accumbens and the striatum of awake, freely moving rats, and to ascertain how this regulation may be affected by desipramine treatment. Somatostatin-14 (10 ±4 M) infusion induced an increase in the release of dopamine and a decrease in the release of its metabolites in both the nucleus accumbens (568% of basal) and the striatum (546% of basal). Chronic desipramine treatment resulted in an exaggerated somatostatininduced increase of dopamine levels, speci®cally in the nucleus accumbens (3542% compared with 564% of basal in the striatum), whereas acute desipramine treatment had no effect (582% of basal) compared with saline treated rats. Basal concentrations of dopamine and metabolites were not in¯uenced by either chronic or acute treatment of desipramine in either brain area. These results demonstrate that somatostatin regulates dopamine release in the nucleus accumbens and the striatum. Chronic antidepressant treatment in¯uences somatostatin's actions on dopamine function selectively in the nucleus accumbens.
Life Sciences, 1999
Expression of the mRNA for somatostatin (SRIF) in the periventricular nucleus (PeN), the level of SRIF in the stalk-median eminence (SME) and the concentration of growth hormone (GH) in the plasma were examined in depressionmodel rats in an attempt to confirm the hypothesis that SRIF neurons in the hypothalamus are hypofunctional in this model. We exposed male Wistar rats to intermittent walking stress for two weeks and then we measured their spontaneous running activity for 12 days. We divided the rats into a depression-model group and a partial-recovery group according to the spontaneous running activity of each rat after the termination of exposure to stress. Expression of SRIF mRNA in the PeN of the hypothalaimus was monitored by in situ hybridization and relative levels were determined with an image analysis system. The relative level of expression of SRIF mRNA in the PeN was lower in rats in the depression-model group than in the control group and the partial-recovery group. The level of SRIF in the SME was lower and the plasma concentration of GH was higher in the depression-model group than in the other groups. Our findings suggest that reduced expression of mRNA for SRIF in the PeN might be associated with the pathophysiology of rats with this particular model of depressia'n.
Depression and Anxiety
Anxiety 8:71-79, 1998.