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T C Rainbow

Publications and source records attributed to T C Rainbow.

69 records · Page 4Linked to original sources
PubMed1982

Regulation of glucocorticoid receptors in brain by corticosterone treatment of adrenalectomized rats.

Binding of (3H)-corticosterone in cytosol of hippocampus and hypothalamus has been measured in adrenalectomized (ADX) rats in the presence or absence of corticosterone replacement therapy (suspended shortly before receptor analysis). Corticosterone pellet implantation into female rats or oral corticosterone administration in salinized drinking water given to males for 3 weeks reduced (3H)-corticosterone binding by half in the hippocampus. This reduction was observed whether corticosterone or dexamethasone was employed as competitor to determine nonspecific binding, thus eliminating transcortin as the cause of the corticosterone effect on binding. Scatchard analysis of binding data revealed that the reduction was mostly due to decreased number of receptors. Animals pretreated with corticosterone had a reduction in thymus weight, indicating further the biological effectiveness of the treatment. Further, serum corticosterone in ADX rats pretreated with corticosterone (but with therapy suspended for 24 h) was very low and similar to that of untreated ADX rats. Uptake studies after injection of (3H)-corticosterone intravenously into ADX rats showed that the injected hormone was absent from blood and brain tissues 1 day later, ruling out (in addition to the measurement of serum corticosterone) that the reduction in binding was due to occupation of receptor sites by exogenous corticosterone remaining after withdrawal from therapy. It is suggested that down-regulation of glucocorticoid receptors in brain follows the chronic corticosterone administration. These data are discussed in relation with evidence for down-regulation of other classes of steroid receptors in several tissues, and the consequence that changes in receptor binding in brain may have on the feedback mechanism of corticoids at the central level.

Adrenalectomy↗
PubMed1982

Progestin receptor levels in rat hypothalamic and limbic nuclei.

We have utilized a method to minimize cytosol progestin receptor loss during freezing in order to localize the quantify estrogen-inducible progestin receptors in individual nuclei of the female rat brain. Ovariectomized females received estradiol benzoate (20 micrograms for 3 days) or vehicle prior to sacrifice. All animals were perfused with cold distilled H2O containing the cryoprotective compound, dimethyl sulfoxide (DMSO; 10% (v/v)). Thirty-one nuclei or brain regions were removed from frozen sections (300 micrometers) according to the method of Palkovits (Palkovits, M. (1973) Brain Res. 59: 449-450) and were assayed in vitro using a synthetic radioligand, [3H]R5020. In ovariectomized animals perfused with DMSO, a basal level (1 to 8 fmol/mg of protein) of progestin receptors was observed in a variety of preoptic, hypothalamic, and limbic structures. Moreover, estrogen treatment induced high levels (24 to 49 fmol/mg of protein) of progestin receptors in regions of the preoptic area of hypothalamus which contain high levels of estrogen receptors. These regions included the medial, periventricular, and superchiasmatic nuclei of the preoptic area, the periventricular anterior hypothalamus, the ventromedial nucleus, and the arcuate-median eminence. Moderate levels (2 to 8 fmol/mg of protein) of progestin receptors were induced by estrogen in other hypothalamic and limbic structures, including the anterior and lateral hypothalamus, the bed nucleus of the stria terminalis, the cingulate cortex, the medial amygdaloid nucleus, and the CA subfield of the hippocampus. By contrast, some areas, such as the caudate-putamen and the supraoptic nucleus, were devoid of both estrogen-inducible and uninduced progestin receptors. These results support the hypothesis that progesterone action in the central nervous system is mediated by cytosol receptors in discrete brain regions and provide the first quantitative map of progestin binding in a vertebrate brain.

Animals↗
PubMed1982

Estradiol receptor levels in rat hypothalamic and limbic nuclei.

The amount of cytoplasmic receptor for the steroid hormone, estradiol (E2), was determined in 46 nuclei and subdivisions of rat brain. Individual nuclei were removed from 300-micrometers frozen sections according to the punch-out method of Palkovits (Palkovits, M. (1973) Brain Res. 59: 449-450), and the content of E2 receptor was measured with a sensitive radioligand binding method. Cytoplasmic receptors for E2 were distributed heterogeneously throughout the rat brain. The highest level of receptor (40 fmol/mg of protein) was found in the periventricular nucleus of the preoptic area, while low (1 fmol/mg) but detectable levels of receptors were found in such limbic regions as the nucleus of the diagonal band, the olfactory tubercle, and the cingulate cortex. Regions that were devoid of detectable receptor included the medial septum, the parietal cortex, and the ventral thalamus. Our results support the notion that E2 influences reproductive behavior and neuroendocrine function by binding to receptors in discrete areas of the brain and provide the first quantitative map of E2 receptors in individual rat brain nuclei.

Animals↗
PubMed1981

Temporal relationship between cell nuclear progestin receptor levels and sexual receptivity following intravenous progesterone administration.

This study was designed to assess the temporal relationship between the appearance and retention of cell nuclear progestin receptors in hypothalamus and the facilitation and decline of feminine sexual behavior following an i.v. injection of progesterone (P). Nuclear translocation of progestin receptors preceded the earliest appearance of behavior. The behavioral effects of P outlasted the nuclear progestin receptor elevation by several hours. Our results are consistent with the idea that P-induced effects on feminine sexual behavior involve genomic activation.

Animals↗
PubMed1980

Studies of memory: a reevaluation in mice of the effects of inhibitors on the rate of synthesis of cerebral proteins as related to amnesia.

Tests were made of the postulates stating that the degree of inhibition of protein synthesis either (a) at training or (b) following training is the critical variable that determines the degree of amnesia. As a first step it was found that the concentrations of numerous cerebral amino acids were substantially increased in 2 strains of mice 0.5 hr after treatment with amnesic doses of the inhibitors of protein synthesis, cycloheximide (CXM) and anisomycin. This observation led, in several different experiments, to a comparison of the apparent degree of inhibition of protein synthesis derived from the acid-soluble radioactivity with that derived from the specific radioactivity of tyrosine tagged with L(1-14C)-tyrosine. In all instances the apparent degree of inhibition was decreased when based upon tyrosine's specific radioactivity. The effect of several treatments with CXM on memory of a 1-trial passive avoidance task provided data for analysis of the relationship between the degrees of amnesia and those of the more accurate estimates of inhibition of protein synthesis based upon the specific radioactivity of tyrosine. The results failed to support the views that the level of inhibition of protein synthesis at or after training are entirely sufficient to account for the behavioral rr indirect change in the brain that antagonizes the amnesic effects of the antibiotic and that consequently contributes to the survival of memory in mice trained 2 hr after a large amnesic dose of CXM.

Amino Acids↗
PubMed1979

Role of RNA and protein synthesis in memory formation.

A brief review is given of experiments which are concerned with the hypothesis that brain RNA and protein synthesis are directly involved in the establishment of long-term memory. It is concluded that these experiments neither support or refute this hypothesis. A convincing demonstration is lacking of interanimal memory transfer by injection of macromolecular extracts. The majority of experiments which attempt to correlate increased macromolecular synthesis with learning use radioactive precursor methods and these studies do not exclude possible changes in precursor specific activity as the cause of the increased labeling. Although some studies find directly observable changes in brain macromolecules in response to training, their relationship to memory formation is unclear. It is possible that these changes represent only an enhanced production of constitutive macromolecules in response to an increase in cerebral metabolism during training, rather than molecular changes that are directly involved with modifying synaptic connectivity. Inhibitors of cerebral protein synthesis block memory formation, but these drugs are not pharmacologically specific and this complicates the interpretation of these studies.

Animals↗
PubMed1979

Distribution, survival and biological effects in mice of a behaviorally active, enzymatically stable peptide: pharmacokinetics of cyclo(Leu-Gly) and puromycin-induced amnesia.

Cyclo(Leu-Gly), the enzymatically resistant diketopiperazine formally derived from the C-terminal dipeptide sequence of oxytocin, exhibits activity in several behavioral systems. The distribution of cyclo(Leu-14C(U)Gly) in brain, and the time course of the disappearance of this labeled peptide from brain and plasma after subcutaneous injection into mice have been studied. The intact peptide was distributed equally in the five cerebral areas studied, for up to 96 hours after injection. Two exponential components were determined for peptide disappearance rates in plasma and brain; peptide half-lives in plasma up to 10 hr and from 24--96 hr after injection were, respectively, 0.8 and 33 hr; in brain, 1.0 and 42 hr. The peptide was found to accumulate in brain intracellular space to some degree. The time course of distribution of labeled cyclo(Leu-Gly) in subcellular fractions of mouse brain was also examined, and the concentration of peptide in the synaptosomal fraction was significantly correlated with the degree of protection against puromycin-induced amnesia of a maze-learning test. The results obtained not only confirm that cyclo(Leu-Gly) penetrates brain tissue intact and remains intact after peripheral administration in order to exert its behavioral effects, but, moreover, suggest an intriguing dynamic relationship between peptide concentration in the synaptosomal fraction and behavioral activity.

Amnesia↗
PubMed1978

Studies on memory: spontaneous return of memory in 6-hydroxydopamine-treated mice and its relation to cycloheximide-induced transient amnesia.

We suggested previously that cycloheximide-induced transient amnesia was due in part to side-effects of the antibiotic on the central adrenergic system at the time of testing and that spontaneous return of memory depended upon recovery of the adrenergic system. To test these possibilities, mice chronically depleted of brain catecholamines (CAs) by 6=hydroxydopamine (6-OHDA) were trained in an avoidance-discrimination task and tested for spontaneous return of memory. Contrary to our hypothesis, amnesia at 24 hr after training was followed by recovery of memory by 72 hr, which indicates that recovery of memory can occur independently of adrenergic recovery. Injection of alpha-methyl-para-tyrosine immediately after training prevented return of memory at 72 hr, suggesting that the residual CAs remaining after 6-OHDA are necessary for memory to spontaneously return at this time.

Amnesia↗
PubMed1978

Inhibition by Z-Pro-D-Leu of development of tolerance to and physical dependence on morphine in mice.

The peptide-Z-Pro-D-Leu, injected daily in mice receiving morphine chronically, was found to prevent development of physical dependence as measured by changes in body temperature and body weight due either to abrupt or to naloxone-induced withdrawal. On the other hand, administration of Z-Pro-D-Leu only on the last day of morphine treatment did not alter the overt signs of withdrawal. Daily administration of Z-Pro-D-Leu was also effective in blocking the development of tolerance to the analgesic and the hypothermic effects of subsequent challenge doses of morphine. However, the peptide treatment did not alter the acute effects of a challenge dose of morphine on either analgesia or body temperature. No effects on memory were noted, as evaluated in a one-trial passive avoidance task. Clinical implications of the use of Z-Pro-D-Leu are discussed.

Animals↗
PubMed1976

Comparison in mice of the amnestic effects of cycloheximide and 6-hydroxydopamine in a one-trial passive avoidance task.

To test further the hypothesis that cycloheximide (CXM)-induced amnesia is due in part to its effects on the central adrenergic system, a comparison was made in mice of the effects of the antibiotic and of 6-hydroxydopamine (6-OHDA) on memory of a one-trial passive avoidance task. Both drugs produced anmesia 24 hr after training but unlike CXM, 6-OHDA had no effect on memory 20 min after training.

Animals↗