The corticosteroid receptor hypothesis of depression.

Glucocorticoid receptors in major depression: relevance to pathophysiology and treatment.

Zinc requirements and the risks and benefits of zinc supplementation

Neurobiological similarities in depression and drug dependence : A self-medication hypothesis

• Considerable evidence suggests that the acute effects of antidepressant treatments on brain norepinephrine (NE) and serotonin (5-HT) systems cannot account fully for their delayed therapeutic action. This review evaluates the effects of long-term antidepressant treatment on biogenic amine metabolism and on various indexes of presynaptic and postsynaptic receptor function. In contrast to variable effects on NE and 5-HT turnover and on presynaptic receptor sensitivity, almost all long-term antidepressant treatments produce consistent alterations in a number of measures of postsynaptic amine receptor sensitivity. Longterm treatment has been found to reduce β-adrenergic sensitivity while enhancing responses to serotonergic and α-adrenergic stimulation, suggesting that modulation of receptor sensitivity may be a mechanism of action common to tricyclic antidepressants, "atypical" antidepressants, monoamine oxidase inhibitors, and electroconvulsive therapy. These findings provide support for hypotheses of amine receptor abnormalities in depression and indicate the need for expanded studies of amine receptor function in patients.

Receptor Sensitivity and the Mechanism of Action of Antidepressant Treatment: Implications for the Etiology and Therapy of Depression

Zinc and Wound Healing Effects of Zinc Deficiency and Zinc Supplementation

Extract: The effect of zinc deficiency on the brain of the suckling rat was studied by feeding a zinc-deficient (Zn-) diet to dams from parturition and measuring the in vivo uptake of 3H-thymidine by brain DNA and the 35S uptake by brain protein as well as the brain lipid composition of their pups. These results were compared with similar data obtained on pups nursed by pair-fed (PF) and ad libitum-fed control dams which had been given zinc in addition to the diet. The specific activities (SA) of DNA and protein were decreased in the brains and livers of the pups nursed by the zinc-deficient dams compared with pups nursed by dams pair-fed with the zinc-deficient dams and hence semistarved (SA of brain DNA: Zn- = 5.90 versus PF = 11.36; SA of liver DNA: Zn- = 5.16 versus PF = 15.8; SA of brain protein: Zn- = 50.20 versus PF = 85.30; SA of liver protein: Zn- = 56.02 versus PF = 79.20). On the other hand, similar concentrations of DNA, RNA, and protein were present in their brains as well as their livers. The concentrations of total lipid were decreased in the brains of the deficient pups compared with the controls (Zn- = 0.215 versus PF = 0.309 mg/mg of brain), while the concentrations of brain phospholipid and the brain fatty acid patterns were similar. Zinc deficiency has thus been shown to impair DNA and protein synthesis in brain of the suckling rat as it has previously been shown to do in other tissues including liver and epiphyseal plate. Speculation: Zinc is essential for synthesis of nucleic acids and protein. In individuals with protiencalorie malnutrition, an associated zinc deficiency may compound the effects of protein deprivation by impairing utilization of the limited protein available. Zinc deficiency in the human may thus contribute to the impaired brain growth reported to occur in infants with protein-calorie malnutrition.

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Zinc deficiency: effect on brain of the suckling rat.

Norepinephrine-independent regulation of GRII mRNA in vivo by a tricyclic antidepressant

Rats with unilateral lesions of the locus coeruleus were used to study the role of norepinephrine (NE) signal input in the down-regulation by antidepressants of the noradrenergic cyclic AMP-generating system in the cortex. Chronic administration of both desipramine (blockade of NE reuptake) and iprindole (no blockade of NE reuptake) reduced the cyclic AMP response to NE on the nonlesioned side, but had little or no effect on the lesioned side. The results indicate that NE signal input and thus the formation of the NE-receptor complex are prerequisites for inducing noradrenergic subsensitivity.

Role of neuronal signal input in the down-regulation of central noradrenergic receptor function by antidepressant drugs.

The present studies were undertaken to characterize further the role of serotonin (5-HT) in the regulation of the norepinephrine (NE) beta adrenoceptor coupled adenylate cyclase system in the rat cortex. Although 5-HT in vitro did not influence maximum binding and Kd values of [3H]dihydroalprenolol binding or the IC50 value for isoproterenol as estimated from competition binding curves in cortical tissue from control animals, 5-HT abolished the increase in beta adrenoceptor number and the marked elevation of the IC50 value for isoproterenol in cortical membrane preparations after selective lesions with 5,7-dihydroxytryptamine (5,7-DHT). Nonlinear regression analysis of competition binding curves revealed that the increase in the maximum binding of beta adrenoceptors after 5,7-DHT is due exclusively to an increase in beta adrenoceptors in the agonist low affinity conformation and that it is this receptor population that is reduced by nanomolar concentrations of 5-HT. The increase in the density of beta adrenoceptors in the low affinity conformation occurred approximately 11 days after the lesions and remained elevated throughout the experimental period of 28 days. Ritanserin in a dose that virtually abolished 5-HT2 receptor binding in cortex did not mimic the effect of 5,7-DHT.(ABSTRACT TRUNCATED AT 250 WORDS)

D. D. Gillespie

Papers

Zinc and Wound Healing Effects of Zinc Deficiency and Zinc Supplementation

Zinc deficiency: effect on brain of the suckling rat.

Norepinephrine-independent regulation of GRII mRNA in vivo by a tricyclic antidepressant

Role of neuronal signal input in the down-regulation of central noradrenergic receptor function by antidepressant drugs.

The serotonin/norepinephrine-link in brain. II. Role of serotonin in the regulation of beta adrenoceptors in the low agonist affinity conformation.