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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Long-Evans female rats were divided into three age groups: 10 young rats (5 months of age), 7 middle-aged rats (10-13 months of age) and 6 old rats (21-27 months of age). The rats were ovariectomized and immediately implanted subcutaneously with a silastic capsule filled with estradiol benzoate (E2). Lordosis response was compared in each animal before and after the septal lesion. Serum E2 levels were 197 +/- 27 pg/ml (mean +/- SEM), 192 +/- 81 pg/ml and 405 +/- 83 pg/ml in young, middle-aged and old rats respectively. When serum E2 levels were adjusted by analysis of covariance, LQ (lordosis quotient) was 42, 36 and 61 in young, middle-aged and old rats respectively before the septal lesion and 98, 68 and 88 respectively after the septal lesion. The extent of potentiation of lordosis after the septal lesion was less in middle-aged and old rats than young rats. These results indicate that an enhanced lordosis response in aged rats is partly due to high circulating E2 levels and partly due to disinhibition of the septal region on lordosis.
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PMID:Effects of septal lesion on lordosis response induced by estradiol in middle-aged and old female rats. 405 52

Self-selected food intake of 15 reduced-obese women living in a metabolic ward was studied for 14 consecutive days to determine the effect of exercise and other metabolic and behavioral variables on energy intake. A choice of prepared food items were offered at breakfast, lunch and dinner, and a variety of additional food items were available continuously 24 h/day. Subjects performed either moderate intensity aerobic exercise (A-EX) (n = 8) expending 354 +/- 76 kcal/session or low intensity resistance weight training (R-EX)(n =7) expending 96 +/- kcal/session, 5 days/week. Mean energy intakes (kcal/day, +/- SEM) of the exercise groups were similar: 1867 +/- 275 for A-EX, 1889 +/- 294 for R-EX. Mean energy intakes of individuals ranged from 49 to 157% of the predetermined level required for weight maintenance. Resting metabolic rate per kg 0.75 and the Eating Inventory hunger score contributed significantly to the between subject variance in energy intake, whereas exercise energy expenditure did not. Regardless of exercise, eight women consistently restricted their energy intake (undereaters), and seven other consumed excess energy (overeaters). Overeaters were distinguished by higher Eating Inventory disinhibition (P = 0.023) and hunger (p = 0.004) scores. The overeaters' diet had a higher fat content 34 +/- 1% (p = 0.007). Also, overeaters took a larger percentage of their daily energy, than that of undereaters, 27 +/- 1 energy intake in the evening, 13 +/- 2%, compared to undereaters, 7 +/- 1% (p = 0.005). We conclude that the Eating Inventory is useful for identifying reduced-obese women at risk of overeating, and these individuals may benefit from dietary counseling aimed at reducing fat intake and evening snacking.
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PMID:Effect of exercise and dietary restraint on energy intake of reduced-obese women. 866 33

Recent experiments have shown that: 1) A chronic 10 month daily administration to rats of the benzodiazepine (BDZ) receptor antagonist, flumazenil (FL; 4 mg/kg in drinking water), from the age of 13 through 22 months, significantly retarded the age-related loss of cognitive functions, as ascertained by the radial arm maze tests conducted two months after FL withdrawal. 2) An equal number of 8 rats died in the control and FL-treated group before the behavioral tests were completed and the animals were sacrificed; the life span of the FL-treated 8 rats equaled 24.0 (+/- 0.6 SEM) months, while that of the control 8 rats equaled 22.3 months (+/- 0.7 SEM), and the group difference was marginally significant (p = 0.04 Mann-Whitney test). 3) In rats sacrificed 3 months after FL withdrawal and behavioral testing, the protective action of FL, relative to age-matched controls, was revealed by a significant reduction in the age-related loss of neurons in the hippocampal formation. 4) In the time period of 3 months between the drug withdrawal and sacrificing of the animals, stress experienced by the aging rats during behavioral testing, related to excessive daily handling of the animals and partial food deprivation to motivate them to perform in the radial arm maze, apparently had excitotoxic effects on the hippocampal neurons, as indexed by the presence of 30% neurons in a state of moderate pyknosis found both in the FL group and the age-matched controls. In the 6 months "young" control group, the number of pyknotic neurons equaled only 3.5%. It was concluded that the drug withdrawal and stress of behavioral testing unleashed the previously FL-controlled age-related degeneration. On the basis of these results and the literature, showing that the tone of the GABAergic system increases with age, and particularly in Alzheimer's disease (AD), the hypothesis of brain aging was formulated. It postulates that in mammals, with growing age, and prematurely in humans with AD, the increasing tone of the BDZ/GABAergic system interferes with antero- and retrograde axonal transport through a chronic depolarizing block of preterminal axon varicosities of the ascending aminergic and cholinergic/peptidergic systems, which are indispensable for normal metabolic/trophic glial-neuronal relationships. Such a state leads to discrete anatomic deafferentation of forebrain systems, and particularly of the neocortex, where block of the anterograde axonal transport results in induction of the cortical mRNA responsible for synthesis of the beta-amyloid precursor protein (beta APP). The simultaneous block of retrograde transport from chronically depolarized preterminal axon varicosities may account for toxic accumulation in cortex of the nerve growth factor (NGF) and other trophins, without which the basal forebrain cholinergic neurons degenerate. The general pharmacologic profile of FL has been discussed on the basis of FL administration to animals and healthy and diseased humans. This profile shows that FL: 1) increases brain metabolic functions; 2) reduces emotional responses, thereby stabilizing the functions of the autonomic system in both humans and animals challenged by adverse environmental stimuli; 3) improves cognitive and coordinated motor functions in both humans and animals; 4) uniquely combines anxiolytic, vigilance and cognitive enhancing, i.e. nootropic, properties, which may, in part, stem from FL-induced emotional imperturbability (ataraxy); 5) facilitates habituation of healthy humans and animals to novel but inconsequential environmental stimuli, and promotes non-aggressive interactions among animals; 6) in single i.v. doses, and administered chronically to humans, FL has antiepileptic actions in the Lennox-Gastaut syndrome and other forms of epilepsy characterized by "spike-and-dome" EEG patterns; these actions are likely to depend on FL's disinhibition of the serotonin system; 7) administered in single i.v...
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PMID:GABAergic deafferentation hypothesis of brain aging and Alzheimer's disease; pharmacologic profile of the benzodiazepine antagonist, flumazenil. 871 36

Opioids are generally believed to activate descending pain inhibitory pathways from the periaqueductal gray matter (PAG). Since opioids exert an inhibitory effect on neural excitability and transmitter release, an opioid-mediated inhibition of tonically active inhibitory gamma-aminobutyric acid (GABA) neurons has been suggested to mediate this effect. The aim of the present microdialysis study was to investigate the effect of local administration of morphine on the extracellular GABA level in the PAG of awake rats. The recently developed and highly sensitive method of capillary electrophoresis with laser-induced fluorescence detection was used for GABA determination in microdialysate samples obtained from the PAG of freely moving rats. The basal GABA level was 54.5 +/- 6.6 nM (n = 8; mean +/- SEM). Perfusion of the dialysis probe with morphine (100 microM) for 30 min significantly decreased the GABA level to 28.2 +/- 4.2 nM (n = 8; P < 0.05). The effect of morphine was reversed by coperfusion with naloxone (100 microM in the perfusion fluid). The present results thus provide direct experimental evidence for an opioid-induced inhibition of tonic GABA release in the PAG, which may in turn lead to a disinhibition of descending pain inhibitory pathways.
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PMID:Local administration of morphine decreases the extracellular level of GABA in the periaqueductal gray matter of freely moving rats. 873 36

A reduction in endogenous opioid inhibition (disinhibition) of GnRH secretion is thought to be permissive for the preovulatory GnRH/LH surge. There are no published studies of the effects of highly specific opioid receptor agonists on the LH surge in any species, and the relative importance of the opioid receptor subtypes mu, delta and kappa in the mechanism of disinhibition is unknown. In sheep, attempts to block the LH surge with opiates have been largely unsuccessful, and there is little evidence for reduced opioid inhibition during the GnRH/LH surge. The opioid receptor subtypes regulating PRL secretion in sheep are also unknown. Conscious, ovariectomized ewes with permanent third ventricular cannulae were injected with estradiol benzoate (EB) 50 micrograms or oil im (t = 0 h). In this model, EB elicits a time-delayed surge in LH secretion after 13-18 h. Jugular venous blood was sampled at half hourly intervals between-2 and 0 h and 10 and 26 h. From 12-20 h, infusions were made into the third ventricle of either the highly specific mu-agonist DAGO (10, 20 or 40 nmol/h), the delta-agonist DPDPE (40 nmol/h), the kappa-agonist U50488 (40 nmol/h) or saline (vehicle). In oil-treated animals (n = 4-6), DAGO infusion at 20 and 40 nmol/h reduced plasma LH whereas DPDPE or U50488 had no effect. In EB-treated animals (n = 6), DAGO (40 nmol/h) delayed the LH surge (mean +/- SEM time to surge onset 21.4 +/- 0.3 h vs. 14.0 +/- 0.4 h in controls, P < 0.0001). DAGO at 10 nmol/h did not alter surge onset and at 20 nmol/h had variable effects. DPDPE or U50488 did not affect LH surge timing or amplitude. All doses of DAGO increased plasma PRL, whereas DPDPE and U50488 had no effect. We conclude that, in ovariectomized ewes, activation of opioid mu-receptors, but not delta- or kappa-receptors, inhibits GnRH secretion, can block the estrogen-induced GnRH/LH surge and increases PRL secretion. The results are consistent with the disinhibition hypothesis.
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PMID:Effects of central administration of highly selective opioid mu-, delta- and kappa-receptor agonists on plasma luteinizing hormone (LH), prolactin, and the estrogen-induced LH surge in ovariectomized ewes. 875 28

Endogenous opioid systems in the hypothalamus inhibit gonadotropin-releasing hormone (GnRH) secretion, and a reduction in this inhibitory input (disinhibition) is thought to be part of the neural mechanism of the preovulatory GnRH/luteinizing hormone (LH) surge. We showed previously that intracerebroventricular infusion of the highly specific opioid mu-receptor agonist DAMGO delayed the oestrogen-induced LH surge in ovariectomized (OVX) ewes, whereas both delta- and kappa-agonists were ineffective. The aim of the present study was to establish the anatomical site of this effect. The most likely hypothalamic sites of action are the medial preoptic area (MPOA), where most GnRH perikarya are located in sheep, and/or the median eminence (ME), where GnRH fibres terminate on hypophysial portal blood vessels. Conscious, unrestrained OVX ewes with permanent bilateral guide tubes implanted into either the MPOA or the mediobasal hypothalamus (MBH), close to the ME, were injected (i.m.) with oestradiol benzoate (EB) 50 microg (t = 0 h). In this model, EB elicits a time-delayed surge in LH secretion after 13-19 h. Jugular venous blood was sampled at half-hourly intervals from -2 to 0 h, and from 10 to 26 h. From 12 to 20 h, bilateral infusions of either the highly specific opioid mu-agonist DAMGO (40 nmol/h bilaterally) or saline were given into the MPOA or MBH at 2.5 microl/h. Guide tube placements were confirmed histologically. The mean (+/- SEM) time to the onset of the LH surge was significantly (p < 0.01) increased in the animals (n = 9) that received DAMGO infusion into the MPOA (20.5 +/- 1.4 vs. 15.7 +/- 0.6 h in the saline-infused controls). The effect was clearly apparent in 6/9 of the DAMGO-infused animals. The mean (+/- SEM) time to LH surge onset was also significantly (p < 0.01) increased in the animals (n = 8) that received DAMGO infusion into the MBH (19.7 +/- 1.2 vs. 14.3 +/- 0.5 h). In this case, the effect was clearly apparent in 4/8 of the DAMGO-infused animals. We conclude that bilateral infusion of DAMGO into either the MPOA or the MBH can delay the EB-induced LH surge in OVX ewes. These data provide further evidence for dual hypothalamic sites of opioid regulation of GnRH secretion, and are consistent with the hypothesis that disinhibition from opioid tone at both the MPOA and MBH/ME is permissive of the preovulatory GnRH/LH surge.
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PMID:Blockade of the oestrogen-induced luteinizing hormone surge in ovariectomized ewes by a highly selective opioid mu-receptor agonist: evidence for site of action. 963 Apr 33

Pairing a cutaneous electrical stimulus of the hind-paw with stimulation of the basal forebrain produces long-term cholinergic enhancement of the responsiveness to a tactile stimulus. A short period of pairing (20 trials) increased the area of the two main components of the evoked potential by 37.1 +/- 13.5% (+/- SEM) and 37.9 +/- 6.8%, respectively. The effects lasted for the duration of the experiment (> 2 h). The enhancement could be blocked by either MK-801, an NMDA receptor antagonist or by L-NAME, a nitric-oxide-synthase inhibitor when they were given prior to pairing. Control experiments with skin stimulation alone and basal forebrain stimulation alone had only small long-term effects (approximately 10%) on the size of the evoked potential. Thus, long-term cholinergic enhancement, attributable to disinhibition and increased release of acetylcholine in the cortex during neuronal excitation by other sources, and so named because it is blocked by atropine, may be a form of long-term potentiation. The existence of such a mechanism for the control of cortical neuronal plasticity identifies the basal forebrain as a powerful modulator of long-lasting changes in cortical neuronal excitability.
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PMID:Long-term cholinergic enhancement of evoked potentials in rat hindlimb somatosensory cortex displays characteristics of long-term potentiation. 1131 Jan 74