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Biomedical subjects

V N Luine

Publications and source records attributed to V N Luine.

At least 19 recordsLinked to original sources

Tianeptine treatment induces regionally specific changes in monoamines.

Tianeptine is an atypical tricyclic antidepressant that facilitates serotonin (5-HT) reuptake. Tianeptine (10 mg/kg) or saline was administered intraperitoneally to male rats daily for 4 days. Monoamine levels were measured in micropunches of discrete brain nuclei that are implicated in mood and cognition. In addition, the rates of 5-HT and norepinephrine (NE) accumulation were determined by the pargyline method. Few changes were noted in the 5-HT system. 5-HT levels were increased by short-term tianeptine in the CA3 region of hippocampus, and 5-hydroxyindoleacetic acid (5-HIAA) was increased in the ventromedial nucleus of hypothalamus, while 5-HT turnover was decreased in preoptic area (POA). In addition, short-term tianeptine treatment increased NE levels in POA, parietal sensory cortex (SCTX) and dorsal raphe (DR), and decreased NE in dentate gyrus. NE turnover was also decreased in DR, SCTX and parietal motor cortex. These data suggest that the short-term neural and behavioral actions of tianeptine may be attributable, in part, to alterations of the norepinephrine system.

Animals

Steroid hormone influences on spatial memory.

Our studies have shown that both stress-induced, enhanced secretion of corticosterone and adrenalectomy-induced, reduced secretion of corticosterone are associated with impaired spatial memory performance. On the other hand, estradiol administration is associated with enhancements in spatial memory performance. Although these changes in performance are small, they are consistent with structural changes induced by these hormones (or their lack) on specific cells within the hippocampus which form the tri-synaptic loop (a summary of the behavioral and morphological effects is shown in Figs. 1 and 2). Thus, these results suggest that the morphological changes induced by the hormones have an impact on hippocampal function. Important goals of future studies are to seek ways to maximize gonadal hormone-dependent enhancements in memory function and to minimize adrenal steroid-dependent impairments in memory function as well as to understand the mechanisms behind these behavioral and morphological changes.

Animals

Effects of adrenalectomy on spatial memory performance and dentate gyrus morphology.

Adrenalectomy (ADX) causes neuronal degeneration and cell loss in the dentate gyrus (DG) of the hippocampus. Since chemical or mechanical lesions of the DG are associated with impairments of spatial memory in rats, the effects of ADX on radial arm maze performance were evaluated. During 15 trials, where all 8 arms of the maze were baited, ADX rats were significantly impaired compared to sham operated controls (Shams). These trials were conducted 21-42 days post-ADX. Following these trials, time delays were instituted between the 4th and 5th choices, and ADX rats continued to show impaired performance. Daily intake of 3% saline was monitored in all rats and serum corticosterone (Cort) was measured. Saline consumption (ml/day) was higher in the ADX group (16.9 +/- 1.6 in ADX vs. 1.3 +/- 0.3 in Shams) and was negatively correlated with Cort level. Serum Cort (% microgram) differed between groups (0.6 +/- 0.4 vs. 15.0 +/- 2.3) and was negatively correlated with a greater number of maze errors, a measure of impaired performance. Cross sectional DG area was not reduced in ADX rats, and pyknotic cell number did not differ significantly between ADX and Sham animals. Moreover, pyknotic cell counts did not correlate with behavioral measures. These results lead to two conclusions: First, the recovery of accessory adrenal tissue in ADX rats, as indicated by the low levels of Cort, appears sufficient to suppress dentate granule neuron pyknosis, but may not be sufficient to suppress salt appetite.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy

Short-term fluoxetine treatment alters monoamine levels and turnover in discrete brain nuclei.

The effects of short-term fluoxetine administration on monoamine levels and turnover were assessed in discrete brain nuclei. Adult male rats received fluoxetine HCl (10 mg/kg) or saline injections intraperitoneally for 4 days and monoamine levels determined by high performance liquid chromatography. The major metabolite of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), was decreased by fluoxetine treatment in the ventromedial hypothalamic nucleus (VMN), the lateral hypothalamic area and the CA1 region of the hippocampus. Fluoxetine treatment significantly increased serotonin (5-HT) levels in the VMN but did not change 5-HT levels in any other area examined. Norepinephrine (NE) levels were higher in fluoxetine-treated rats in the dorsomedial hypothalamic nucleus, dorsal raphe nucleus and parietal motor cortex (MCTX). 5-HT and NE turnover were also determined by the pargyline method. Fluoxetine treatment decreased 5-HT turnover in the VMN and increased 5-HT turnover in the median raphe. NE turnover was decreased in the preoptic area, the MCTX and parietal sensory cortex by fluoxetine administration. These results demonstrate that brain areas with similar 5-HT innervation respond differently to fluoxetine administration and fluoxetine, which selectively alters 5-HT uptake, also affects NE levels and turnover in several brain nuclei.

Animals

Serotonergic lesions decrease mu- and delta-opiate receptor binding in discrete areas of the hypothalamus and in the midbrain central gray.

Serotonergic nerve terminals in the brain were lesioned by intraventricular infusion of the selective neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) and levels of mu- and delta-opiate binding were measured in brain areas implicated in reproductive behavior and gonadotropin secretion. The lesion decreased mu-receptor binding in the preoptic area (mPOA) and the midbrain central gray, while delta-receptor binding was decreased in the mPOA and the dorsomedial nucleus of the hypothalamus. Hypothalamic serotonergic lesions also attenuated morphine inhibition of female sexual behavior. These results indicate the existence of serotonergic-opiate interactions in select regions of the brain and suggest that these interactions may be important in the regulation of lordosis behavior.

Animals

Effects of chronic corticosterone ingestion on spatial memory performance and hippocampal serotonergic function.

The effects of chronic ingestion of corticosterone (8 weeks via the drinking water, 400 micrograms/ml) on spatial memory performance and on monoamine levels in brain areas related to memory were investigated. Corticosterone treatment was associated with a long lasting (5 weeks post treatment) increase in 5-HT levels (44%) in the dentate gyrus of the hippocampus and decrease in 5-HT (50%) and NE (36%) levels in the frontal cortex. No effects were found in CA1, CA3 or in nucleus basalis. Performance of the rats on an 8-arm radial arm maze showed no overall effect of corticosterone treatment on trials to criterion or choice accuracy scores. However, three of the treated rats, who had consumed the most corticosterone during treatment, 12.5 +/- 0.3 mg/day, were impaired relative to all subjects. Thus, these results suggest that hippocampal serotonergic terminals show long lasting effects from corticosterone and may also be an early indicator of deleterious effects of glucocorticoids on hippocampal function. However, since only a small number of corticosterone-treated rats showed behavioral changes, future experiments are necessary to address the possibility that a higher level of corticosterone intake alters spatial memory as well as brain morphology and neurochemistry. Additional studies are also needed to determine whether such changes represent a threshold effect of the steroid or a dose-response function.

Administration, Oral

Pargyline-induced increase in serotonin levels: correlation with inhibition of lordosis in rats.

The effect of intrahypothalamic infusion of the monoamine oxidase inhibitor pargyline on lordosis behavior and monamine levels in the preoptic area and hypothalamus was examined. Progesterone-facilitated lordosis was blocked by pargyline in half the treated rats. The inhibition of lordosis was correlated with increases in serotonin and dopamine levels in the ventromedial nucleus of the hypothalamus and serotonin levels in the arcuate nucleus-median eminence when compared to controls or pargyline-treated rats with high levels of lordosis responding. Changes in norepinephrine levels were not correlated with changes in behavior. The results provide further evidence for an inhibitory role of basomedial hypothalamic serotonin in the control of female sexual behavior.

Animals

Serotonin, catecholamines and metabolites in discrete brain areas in relation to lordotic responding on proestrus.

Levels of serotonin (5-HT) and metabolite, 5-hydroxyindole-acetic acid (5-HIAA), dopamine and metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and norepinephrine (NE) were measured in microdissected brain areas at 14.30 and 19.30 h on diestrus and proestrus in rats. Lordosis, sexual behavior, was exhibited only by proestrous females at 19.30 h. The content of monoamines and/or metabolites changed from afternoon to early evening of diestrus in a number of brain regions. On proestrus, during the time when females became sexually receptive, additional changes appeared and many diestrous changes were reversed or amplified. Proestrus-specific changes were found in areas providing the descending circuit for regulation of lordosis, the medial preoptic nucleus (mPOA), ventromedial nucleus of the hypothalamus (VMN) and midbrain central gray (MCG), and in areas outside of endocrine control centers such as parietal cortex (Ctx) and dorsal raphe nucleus (DR). Thus, these data are consistent with previous studies showing functional changes in monoaminergic transmitters during the day/night cycle and during hormonal induction of neuroendocrine events. NE levels increased between 14.30 and 19.30 h on proestrus in most brain areas, ranging from 20% increases in mPOA and Ctx to a 220% increase in the DR. NE levels decreased on proestrus in the VMN. The direction of proestrous changes in NE were reversed in some, but not all of the areas, between the afternoon and evening of diestrus. Dopamine was detectable in all areas sampled, and the metabolites HVA and DOPAC were detectable in some but not all areas.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Sexual behavior of male rats is differentially affected by timing of perinatal ACTH administration.

The laboratory rat was used as a model to investigate the effect of pre- and/or postnatal ACTH administration on sexual differentiation of the brain. Pregnant Sprague-Dawley rats were injected with ACTH 1-24 (10 micrograms/kg/2x/day or 500 micrograms/kg/2x/day); postnatally treated neonates were injected with the above dosages once a day. Perinatal treatment with ACTH (10 micrograms/kg/2x/day) altered several sexual behavior measurements, but did not have an overall effect on the number of males that exhibited sexual behavior. At a higher dose (500 micrograms/kg/2x/day) prenatal ACTH administration decreased sexual behavior in male rats, as measured by an increase in the percent of males that did not mount or intromit. In contrast, all males treated postnatally with ACTH (500 micrograms/kg/2x/day) completed 2 ejaculatory series and initiated a third series. No significant differences were observed in adult plasma testosterone or prolactin levels; however, serotonin levels in the preoptic area of adult male rats treated prenatally with ACTH (500 micrograms/kg/2x/day) were significantly higher than in prenatally treated saline males. In addition, an increase in plasma ACTH in adulthood was observed in animals injected postnatally with saline. This study indicates that the decrease in sexual behavior observed in males treated prenatally with ACTH is associated with increased serotonin levels in the preoptic area, which suggests that ACTH may act as a neuromodulator during sexual differentiation of the brain. It also demonstrates that the effect of perinatal manipulations on the development of male sexual behavior may vary depending on the ontogenetic period of the brain.

Adrenocorticotropic Hormone

Testosterone locally increases vasopressin content but fails to restore choline acetyltransferase activity in other regions in the senescent male rat brain.

Age-related decreases have been reported in both vasopressinergic and cholinergic innervation in the rat brain. Since both systems are also sensitive to sex steroids, the effect of testosterone supplementation on vasopressin (AVP) levels and on choline acetyltransferase (ChAT) activity was investigated in the brains of young, middle-aged and aged male rats. Although no age-related changes in AVP levels were observed in the lateral septum or the medial amygdala (MA), peripheral testosterone administration raised AVP levels in the MA in all age groups. ChAT activity decreased with age in the medial preoptic area and was not restored by testosterone.

Aging

Corticosterone-dependent alterations in utilization of catecholamines in discrete areas of rat brain.

This study investigated the impact of chronic adrenalectomy (ADX), and subsequent corticosterone (CORT) replacement to ADX rats, on brain levels of norepinephrine (NE) and dopamine (DA) and their extent of depletion after alpha-methyl-p-tyrosine (alpha-MpT) administration. Seven discrete hypothalamic areas, namely, the paraventricular nucleus (PVN), medial preoptic nucleus (POM), dorsomedial nucleus (DMN), ventromedial hypothalamus (VMH), perifornical lateral hypothalamus (PLH), supraoptic nucleus (SON), and arcuate nucleus/median eminence (ARC-ME), were examined. The steady-state content of NE and DA in all areas remained essentially unaltered 7 days after ablation of the adrenal glands, as well as after subsequent CORT replacement therapy in ADX rats. However, ADX, which reduced circulating CORT levels to 0.3 microgram % as compared to greater than 3.0 micrograms % in sham rats, caused a significant increase in the depletion of NE following alpha-MpT treatment, in 4 out of the 7 brain sites examined (PVN, PLH, DMN and ARC-ME). In these brain sites, the NE turnover rate (K, pg/microgram protein/h) and rate constant (K, h-1) increased following ADX. The chronic subcutaneous CORT implant (200 mg), which raised circulating CORT levels of ADX rats to 11 micrograms %, prevented this enhancement of NE turnover in the PVN, PLH and ARC-ME, but not the DMN. Unlike NE, DA utilization in the 7 discrete hypothalamic areas of alpha-MpT-treated rats remained unaltered after ablation of the adrenal glands, as well as after the CORT replacement therapy in ADX rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy

Antibodies in serum of patients with Alzheimer's disease cause immunolysis of cholinergic nerve terminals from the rat cerebral cortex.

A blind study showing that serum from patients with Alzheimer's disease causes immunolysis of mammalian brain synaptosomes is reported. Control, aged-matched, sera were largely without effect. The immunolysis was directed mainly against cholinergic synaptosomes. The data support the hypothesis that autoimmune mechanisms may operate in the pathogenesis of Alzheimer's disease.

Aged

Evidence for the presence of antibodies to cholinergic neurons in the serum of patients with Alzheimer's disease.

A blind study showing that serum from patients with Alzheimer's disease causes immunolysis of mammalian brain synaptosomes is reported. Control, aged-matched, sera were largely without effect. The immunolysis was directed mainly against cholinergic synaptosomes. The data presented support the hypothesis that autoimmune mechanisms may operate in the pathogenesis of Alzheimer's disease.

Aged

Hypothalamic serotonin lesions unmask hormone responsiveness of lordosis behavior in adult male rats.

Hypothalamic lesions of serotoninergic afferents following bilateral stereotoxic injections of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) into the region of the ventromedial hypothalamus enhanced the effects of hormonally induced lordosis responding in both male and female rats. However, similarities and differences in the enhanced responsiveness to ovarian hormones were observed between the sexes. Compared with sham-lesioned controls, lesioned males displayed elevated lordosis responding to estradiol (E) priming alone, as well as to priming with E followed by progresterone (P). On the other hand, lesioned females displayed elevated lordosis in response to E priming alone, but were not different from controls in a synergistic facilitation of lordosis by P after E priming. With respect to receptivity, neither lesioned nor control males displayed ear-wiggling and hop-darting in response to E + P, whereas both lesioned and control females were proceptive following this treatment. Therefore, hypothalamic lesions following 5,7-DHT increase lordosis, but fail to unmask in males the responsiveness to E + P priming proceptive behaviours by females. Further, the levels of lordosis responding displayed by lesioned males are lower than those of either lesioned or control females after E + P priming, as well as those of lesioned females after E priming alone, thus indicating that other inhibitory mechanisms continue to operate in the lesioned males.

Animals

Effects of hypothalamic serotonin depletion on lordosis behavior and gonadal hormone receptors.

The effects of chronic depletion of serotonin on feminine sexual behavior (lordosis), cytosolic progestin receptors and estradiol nuclear receptors were investigated. Intrahypothalamic administration of 5,7-dihydroxytryptamine (5,7-DHT) markedly enhanced lordotic responding in estradiol benzoate (EB)-primed, 5,7-DHT-treated female rats and in EB-progesterone primed, 5,7-DHT-treated male rats. Cytosolic progestin receptors were measured in preoptic-hypothalamic nuclei related to reproductive function in sham and 5,7-DHT-treated rats after EB priming. In both sexes, no differences between sham and 5,7-DHT-treated subjects were noted for progestin binding in the medial preoptic nucleus, ventromedial nucleus or arcuate-median eminence area. Estrogen-nuclear complexes were measured in the same brain nuclei of female rats following EB priming, and no differences between sham and 5,7-DHT-treated rats were found. Under the conditions employed, it would appear that, despite marked elevations in lordotic responsivity, the accumulation of estrogen nuclear receptors and the levels of estrogen inducible progestin receptors remain unaltered after chronic depletion of serotonin. Thus, serotonergic influences on lordosis do not appear to involve changes in the expression of steroid receptor levels in preoptic-hypothalamic nuclei known to mediate hormone-dependent neuroendocrine processes.

5,7-Dihydroxytryptamine

Temporal effects of intrahypothalamic 5,7-dihydroxytryptamine: relationship between serotonin levels and [3H]serotonin binding.

The relationship between serotonin (5-HT) levels and [3H]5-HT binding in discrete hypothalamic areas was examined in separate groups of animals at various times, following unilateral intrahypothalamic injection of 5,7-dihydroxytryptamine (5,7-DHT). Seven days post-5,7-DHT lesion, 5-HT levels were significantly decreased in both the ipsilateral and contralateral ventromedial and dorsomedial hypothalamic nuclei (VMN, DMN). In the lateral hypothalamic area (LHA), 5-HT levels were significantly decreased only ipsilaterally. Fifty days postlesion, 5-HT levels in the ipsilateral VMN remained significantly below sham, while the DMN and LHA returned to sham values. Seven days after 5,7-DHT there was a significant increase in [3H]5-HT labeling densities in the ipsilateral and contralateral ventromedial hypothalamic area as well as in the ipsilateral LHA. In contrast, in the dorsomedial hypothalamic area there was no increase in [3H]5-HT binding. Fifty days postlesion, no significant differences in [3H]5-HT binding between 5,7-DHT and sham were observed in any areas examined. This data provides further evidence for the regeneration of 5-HT fibers in the hypothalamus and demonstrates that the relationship between [3H]5-HT binding and 5-HT levels varies from one hypothalamic area to another.

5,7-Dihydroxytryptamine