Effect of stress on sulfated glycol, metabolites of brain norepinephrine.

The present study examined the effect of footshock stress on the formation of the two major metabolites of rat brain norepinephrine (NE) - the sulfate conjugates of 3-methoxy-4-hydroxyphenylglycol (MOPEG-SO₄) and 3,4-dihydroxyphenylglycol (DOPEG-SO₄). Rats receiving intraventricular injections of either ³HNE or Na₂³⁵SO₄ prior to 0.5 hour of footshock showed significant and comparable increases in both sulfated glycols labeled with ³H or ³⁵SO₄. Elevations were greatest in the hypothalumus using Na₂³⁵SO₄. In pheniprazine pretreated rats footshock did not increase the production of MOPEG-³⁵SO₄ from intraventricular labeled sulfate given alone or in combination with various doses of exogenous MOPEG. The results indicate that neuronally released brain NE is metabolized to form both MOPEG-SO₄ and DOPEG-SO₄. The increase in these metabolites results from an increased glycol production and not from a stress-induced activation of brain sulfation mechanisms.     

Naloxene enhances stress-induced increases in noradrenaline turnover in specific brain regions in rats

Male Wistar rats were injected subcutaneously with either saline or naloxone, 1 mg/kg or 5 mg/kg, 10 min before exposure to 1-hour immobilization-stress. Control animals were sacrificed 70 min after respective injections. Levels of noradrenaline (NA) and its major metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO₄) in seven discrete brain regions and plasma corticosterone levels were fluorometrically determined. Immobilization stress caused significant elevations of plasma corticosterone which were not affected by pretreatment with naloxone. In the hypothalamus, amygdala and thalamus, immobilization-stress caused significant elevations of MHPG-SO₄ levels, and naloxone at 5 mg/kg significantly enhanced these stress-induced elevations virtually without affecting the basal level of the metabolite. In contrast, in the hippocampus, cerebral cortex and pons plus medulla oblongata, MHPG-SO₄ levels were elevated by stress, but were not affected by naloxone pretreatment. The effect of naloxone on stress-induced reductions of NA levels was unclear, since naloxone by itself (5 mg/kg) significantly decreased the amine levels in 5 of 7 brain regions examined. These results indirectly suggest that endogenous opioid peptides in the hypothalamus, amygdala and thalamus are partly involved in the stress process and attenuate increases in NA turnover induced by stress.     

The influence of vasoactive intestinal polypeptide and cholecystokinin of prolactin release in rat and human monolayer cultures

We have evaluated the effects of the gut-brain peptides, VIP and CCK, on pituitary PRL secretion in monolayer cultures of normal and tumor bearing rodent and human pituitary tissue. In cultures prepared with normal human pituitary tissue obtained from three patients with metastatic breast cancer, VIP at 10^?7M and 10^?9M (but not 10^?11M) significantly (p<.05) increased PRL secretion in the wells by 6 hrs. Similar concentrations of VIP also significantly (p<.05) promoted PRL release from pituitary tissue obtained by transphenoidal hypophysectomy from one of two prolactinoma patients. Dopamine (10^?5M) inhibition of PRL secretion was not affected by 10^?11 to 10^?7M VIP. In contrast to these findings VIP did not significantly influence 6 hr rat PRL release in monolayer cultures of normal or transformed cells (GH₃) with or without the addition of bacitracin (10^?5M).CCK₃₃ significantly (p<.01) increased rat PRL release in human pituitary monolayer cultures at 10^?5M. The more biologically potent CCK₈ significantly (p<.02) increased rat PRL release at a 10-fold lower concentration, 10^?6M. In contrast, CCK₈ 10^?8 to 10^?6M, did not significantly influence PRL release from normal human pituitary cultures or from tumor bearing human (prolactinoma) and rat (GH₃) cultures. We conclude that 1) the gut-brain peptides, VIP and CCK, can directly stimulate pituitary PRL release and 2) VIP may be a physiologic prolactin releasing factor in man.     

Rapid block of gonadotropin uptake by corpora lutea in vivo induced by prostaglandin F2α

Intravenous administration of ¹²⁵I-hCG to 7–8 day pseudopregnant rats resulted in maximum uptake of radioactivity to corpora lutea 2 hours after treatment. At this time tissue/plasma radioactivity ratios on an equal weight basis were: corpora lutea, 70.2 ± 12.8; ovarian interstitium, 4.6 ± 0.2; kidney, 2.2 ± 0.1. No appreciable uptake was seen by adrenals or liver. Radioactivity in corpora lutea was associated primarily with membranes which sedimented at 2000g and when released by heat it was more than 63% bound to luteal LH receptor preparation in vitro. Radioactivity in renal tissue was associated primarily with the 100,000g supernatant fraction and was bound less than 1% to luteal LH receptors in vitro.PGF₂α significantly reduced uptake (p<.001) of ¹²⁵I-hCG by corpora lutea within 30 minutes (?63%) as well as at 1 (?64%), 2 (?75%), 4 (?68%) and 24 hours (?85%). No clear effect of PGF₂α on uptake of ¹²⁵I-hCG by ovarian interstitial tissue was seen. Plasma progesterone was significantly decreased (p<.001) within 30 minutes (?47%; p<.01) after PGF₂α treatment and also at 1 (?65%), 2 (?82%), 4 (?68%) and 24 hours (?92%). Two hours after PGF₂α treatment the content of progesterone in corpora lutea was depressed (?46%; p<.001). It is suggested that the rapid inhibition of luteal progesterone production induced by PGF₂α in vivo occurs through a block in gonadotropin uptake by corpora lutea.     

The effects of acute and chronic morphine treatment and of morphine withdrawal on rat brain in vivo

1. The effects of morphine, nalorphine, acetazolamide, and 10% CO₂ on brain metabolite concentrations of 24h-starved rats were studied. 2. A single dose of morphine (20mg/kg body wt.) caused an increase in brain glucose concentration (42%) and decreased concentrations of lactate (24%), pyruvate (29%), citrate (20%), α-oxoglutarate (16%), malate (14%) and creatine phosphate (10%) after 30min. No changes were found in adenine nucleotide concentrations. 3. The same dose of morphine increased arterial CO₂ from 5.07 to 7.60 kN/m² (38 to 57 Torr), decreased the pH from 7.41 to 7.31 and decreased O₂ from 14.1 to 10.8kN/m² (106 to 81 Torr) at 30min. 4. Rats injected with morphine three times daily (20mg/kg body wt.) for 2 weeks had no changes in brain metabolite concentrations or in blood gases 30min after their last injection. 5. Nalorphine (an antagonist of morphine) caused essentially no changes in brain metabolite concentrations in normal rats. When nalorphine (20mg/kg) was administered to rats previously treated with morphine three times daily for 2 weeks, there was an increase in brain glucose (100%), lactate (23%), pyruvate (18%) and citrate (10%) concentrations. 6. Acetazolamide (an inhibitor of carbonic anhydrase) and 10% CO₂ increased the arterial CO₂ from 4.79 to 6.78kN/m² (36 to 51 Torr) and from 5.32 to 10.8kN/m² (40 to 81 Torr) respectively. 7. Both acetazolamide and 10% CO₂ caused changes in brain metabolite concentrations similar to those for acutely administered morphine. Thus 10% CO₂ caused increased brain glucose concentration (123%) and decreased brain lactate (46%), pyruvate (34%), citrate (26%), α-oxoglutarate (33%), malate (45%) and creatine phosphate (7%) concentrations. No changes in adenine nucleotide concentrations were found. 8. The results indicate that the effect of morphine on brain metabolite concentrations may be accounted for by the increased [CO₂]. 9. These findings constitute a consistent pattern of metabolic changes after acute morphine administration, morphine addiction, and withdrawal from morphine addiction.     

The synthesis of N-acetyl-leukotriene E4 and its effects on cardiovascular and respiratory function of the anesthetized pig

The effects of the putative bilary metabolite of the peptidoleukotrienes, N-acetyl-leukotriene (LT) E₄ has been investigated in the anesthetized pig. Intravenous bolus doses of synthetic N-acetyl-LTE₄ produced minimal respiratory and cardiovascular actions in the pig. N-acetyl-LTE₄ was approximately 100-fold less active than LTC₄. The actions of N-acetyl-LTE₄ were not blocked by pretreatment of the animals with indomethacin (5 mg/kg iv) or with a selective LTD₄ antagonist L-649,923 (5 mg/kg plus 2 mg/kg/hr iv). In summary, N-acetyl-LTE₄ exerts weak actions in the pig which is consistent with the acetylation process being a mechanism of detoxification.     

Effects of prostaglandin on estrous cycles,behavior and blood progesterone levels of American Saddlebred mares

Twelve American Saddlebred mares ranging in weight from 365 to 450 kg were given intramuscular injections of 2.5, 5.0 and 7.5 mg of Prostaglandin (PGF_2α) on day 6 of diestrus a mean length of control estrus and diestrus were 6.5 ± .6, 16.9 ± 1.0 days, respectively. The 2.5, 5.0 and 7.5 mg PGF_2α doses significantly (P < .01) shortened the length of the treatment diestrus to 10.8 ± 1.8, 9.9 ± .7 and 9.9 ± .7, respectively. The 2.5 mg dose was 90% effective in shortening the duration of diestrus while doses of 5.0 and 7.5 mg were 100% effective. No effects were noted on the mean length of estrus or diestrus following treatment. Peripheral plasma progesterone concentrations were measured by radioimmunoassay to determine the luteolytic effect of PGF_2α. As compared to the non-treatment estrous cycles, all three treatments caused a significant (P < .01) decline in peripheral plasma progesterone concentrations 24 and 48 hr after treatment. The 2.5 mg PGF_2α dose caused a drop in progesterone from 7.7 ± .4 on day 6 to 2.6 ± 1.0 and 2.1 ± .9 ng/ml 24 and 48 hr later, respectively. Similarly, 5.0 mg lowered the progesterone level from 7.7 ± .3 to 1.6 ± .6 and 1.5 ± .5 ng/ml, and the 7.5 mg dose lowered the progesterone level 7.5 ± .3 to 1.2 ± .2 and 1.3 ± .3 PGF_2α. Abdominal cramps were noted in some mares after treatment. The incidence and severity of these reactions increased with the dose of PGF_2α.     

Anticonvulsant effects of magnesium sulfate in hippocampal-kindled rats

The objective of the present study was to determine whether magnesium sulfate has anticonvulsant actions in the hippocampal-kindled rat model of epilepsy. Fully kindled rats received acute intraperitoneal injections of magnesium sulfate (270 mg/kg), phenytoin (20 mg/kg) or saline in random order. Electrical seizure duration, behavioral seizure stage and duration of postictal EEG depression were examined 15, 30 and 60 min after injection. In an additional group of rats, kindled seizures were measured before and after chronic (2 h) intraperitoneal injections of magnesium sulfate versus saline. There was a significant decrease in electrical seizure duration (p<0.01) and behavioral seizure stage (p<0.01) with acute magnesium sulfate injections compared to saline injections. Phenytoin had no statistically significant effects on hippocampal-kindled seizures. Chronic magnesium sulfate treatment significantly reduced behavioral seizure stage at 2, 24, and 48 h postinjection (p<0.05), but did not affect seizure duration. There was a significant time by treatment effect for magnesium sulfate on postictal EEG depression (p<0.01). We conclude that in this model of hippocampal epilepsy-induced (kindled) rats, magnesium sulfate has significant anticonvulsant effects.     

Corpus luteum function in the ewe: Effect of PGF2α and prostaglandin synthetase inhibitors

A series of experiments were conducted to evaluate the effects of mode and frequency of administration and estrous cycle stage on the response of the cycling ewe to PGF_2α. The effects of dexamethasone, arachadonic acid and prostaglandin synthetase inhibitors on estrous cycle length and plasma progesterone levels were also determined.Intramuscular administration of 5 or 10 mg of PGF_2α, on days 8 and 9 after estrus (5 ewes/group), significantly (p<.01) shortened the mean length of the estrous cycle and the interval from the end of treatment to estrus. Mean plasma progesterone levels, 24 hours after initial injection, were significantly (p<.01) lowered. When administered on day 8 only, these doses were considerably less effective in shortening estrous cycle length or lowering plasma progesterone levels. Intravaginal administration of PGF_2α, by polyurethane tampon, was also largely ineffective.Treatment of ewes with 10 mg of PGF_2α i.m., on days 3 and 4 of the estrous cycle, resulted in a return to estrus in 2 days in 25% of the treated animals. Plasma progesterone levels of PGF_2α-treated ewes were significantly lower than controls on the second, third and fourth days after the start of dosing. It would appear that PGF_2α exerts a retarding effect on developing CL functionality.The prostaglandin synthetase inhibitors, aspirin, flufenamic acid and 1-p-chlorobenzylidene-2-methyl-5-methoxy-3-indenylacetic acid, were administered orally or parenterally for 16 days beginning on day 8 of the estrous cycle. These compounds failed to prolong estrous cycle length. Parenteral administration of dexamethasone did not result in PGF_2α release in the cycling ewe, at least not in quantities sufficient to induce luteolysis. The prostaglandin precursor, arachadonic acid, also was not luteolytic when given parenterally to cycling ewes.     

Effects of morphine-3-glucuronide on the antinociceptive activity of peptide and nonpeptide opioid receptor agonists in mice

The effects of morphine-3-glucuronide (M3G), a metabolite of morphine, were determined on the antinociceptive actions, as measured by the tail flick test, of morphine, a μ-opioid receptor agonist, of U-50,488H, a κ-opioid receptor agonist, of [ -Pen², -Pen⁵]enkephalin (DPDPE), a δ₁-opioid receptor agonist, and of [ -Ala²,Glu⁴]deltorphin II (deltorphin II), a δ₂-opioid receptor agonist in mice. Morphine administered ICV (2.5 μg/mouse) or SC (10 mg/kg), U-50,488H (25 mg/kg, IP), DPDPE (15 μg/mouse; ICV), and deltorphin II (15 μg/mouse, ICV) produced antinociception in mice. Intraperitoneal or ICV injections of M3G did not produce any effect on the tail flick latency nor did it affect the antinociception-induced by morphine, U-50,488H, DPDPE, or deltorphin II. Previously M3G has been shown to antagonize the antinociceptive effects of morphine in the rat. It is concluded that in the mouse, M3G neither produces hyperalgesia nor modifies the actions of μ-, κ-, δ₁-, or δ₂-opioid receptor agonists.     

Effect of corticoid induced parturition on lactation and on prepartum profiles of serum progesterone and the estrogens among cows retaining and not retaining fetal membranes

Twenty-one mature F1 Brahman-Hereford cows were treated with 25 mg of dexamethasone (DEX) on day 279 or 280 of gestation to induce birth prematurely. Eigth cows were untreated (UT). Blood was sampled on day 279 or 280 of gestation just prior to treatment of cows with DEX (0 hr), at least daily thereafter to calving and within 1 hr postpartum. Concentrations of progesterone (P₄), estrone (E₁) and estradiol-17β (Eβ) and -17α (Eα) in blood serum were measured by radioimmunoassay. Among 21 cows treated with DEX, 16 (76%) calved within 78 hr (52±3 hr). Eleven of the 16 cows retained fetal membranes more than 12 hr (RFM) and five cows did not retain fetal membranes (NRFM). Five cows (24%) treated with DEX calved 266±46 hr later (NOR) on day 290±1 of gestation compared to day 286±2 for cows in group UT. No cow in groups NOR or UT had RFM. Failure of group NOR to calve prematurely appeared due to elevated serum P₄ (P<.05), low serum Eβ (P<.10) and other estrogens (P>.10) pretreatment, and to only a 32% decrease in serum P₄ within 72 hr after treatment. Serum estrogens, especially Eβ, were next lowest pretreatment in group RFM. However, in group RFM, all serum estrogens increased (P<.10 to P<.01) within 48 hr after treatment, reached higher concentrations and peaked later in relation to calving than in other groups (NRFM, NOR and UT). Synchronization of placental maturation and parturition may require a longer period of elevated serum estrogens prior to calving than was observed in group RFM. Treatment of cows prepartum with DEX had no effect on gain of calves, milk yield or yields of fat, total protein and total solids in milk during the first 12 weeks of lactation.     

The effect of pentobarbital on the antinociceptive action of morphine in morphine-tolerant and non-tolerant rats

The interaction of sodium pentobarbital with morphine sulfate in both morphine-tolerant and non-tolerant rats was investigated using the tail-compression test for analgesia. Male Sprague-Dawley rats (300–350 g) were given pentobarbital (4, 8, or 16 mg/kg) 5 min before morphine (2, 4, 6, or 8 mg/kg). Control animals received two saline injections, or pentobarbital plus saline, or saline plus morphine. All injections were subcutaneous. Prior to the first injection, a baseline nociceptive threshold was determined for each rat by applying a modified micrometer to its tail and increasing the pressure until a squeak was elicited. Test readings were taken every half-hour for 2 hr beginning 30 min after the second injection. For the chronic studies, animals were first made tolerant to morphine by the administration of the narcotic twice a day for 3 days, increasing the dose from 10 to 50 mg/kg/injection. Identical testing procedures were then followed with these rats except that the test dose of morphine given on day 4 was in the range 8–128 mg/kg. It was found that Na pentobarbital, in the subanesthetic doses used, had neither antinociceptive nor hyperalgesic properties. Furthermore, the barbiturate had no effect on the antinociceptive action of morphine in either morphine-tolerant or non-tolerant rats.     

Antagonistic effect of buprenorphine on the antitussive effect of morphine is mediated via the activation of μ1-opioid receptors

The effect of buprenorphine on the antitussive effect of morphine was examined in mice. Buprenorphine at doses of 0.1,0.3 and 1 mg/kg given i.p. alone have no effects on the % inhibition in the number of capsaicin-induced coughs. However, pretreatment with the same doses of buprenorphine for 2 hr significantly attenuated the antitussive effect of morphine (3 mg/Kg, I.p.). Naloxonazine, a selective μ₁-opioid receptor antagonist, had no effect on the antitussive effect of morphine, but blocks the antagonistic effect of buprenorphine on antitussive effect of morphine. These results suggest that buprenorphine antagonizes the antitussive effect of morphine via the activation of μ₁-opioid receptors.     

Is there an opiate receptor in the snail Megalobulimus sanctipauli? Action of morphine and naloxone

The effects of morphine sulfate (10, 15 and 20 mg/kg) or saline control (5 mg/kg) on the latency of the anterior body-lifting response to heat (avoidance response) were determined in four groups of snails Megalobulimus sanctipauli (n = 6) individually placed on a metal plate mounted on the surface of a water bath at 52 ± 1°C. The effects of pre-treatment with naloxone hydrochloride (5 mg/kg) or saline (2.5 ml/kg) control on the responses to morphine (15 mg/kg) were determined in two different groups of animals (n = 6). Administration of morphine resulted in an increase in the avoidance behavior latency with maximum effects occuring at 15 mg/kg, 10–15 min after injection. The effects of morphine disappeared within 90–120 min. Saline treatment had no detectable effects on the latency of the response to an aversive stimulus. Naloxone significantly blocked (P < 0.05, Student paired t-test) the increase in avoidance behavior latency. The present results indicate that: 1. morphine has an antinociceptive effect on the response of Megalobulimus sanctipauli to an aversive thermal stimulus; and 2. the morphine-induced “analgesia” may be caused by the stimulation of μ opiate receptors.     

Physiological control of brain norepinephrine synthesis by brain tyrosine concentration

The intraperitoneal administration of tyrosine to rats causes proportional increases in brain tyrosine levels and in the accumulation of the norepinephrine metabolite 3-methoxy-4-hydroxy-phenylethyleneglycol-sulfate (MOPEG-SO₄) after probenecid. Brain tyrosine level after tyrosine administration or after the consumption of a single meal is also positively correlated with brain MOPEG-SO₄ accumulation in rats that do not receive probenecid but are subjected to cold stress. These observations extend our earlier finding that brain tyrosine level can affect the rates at which catecholaminergic neurons synthesize and turn over their transmitters.     

Evidence of possible opiate dependence during the behavioral depressant action of a single dose of morphine

Rats were trained to lever press for food pellets under a 20 response fixed ratio (FR 20) schedule of reinforcement. A single injection of 15 mg morphine SO₄/kg suppressed operant behavior for $\text{1}\text{1}\text{2}\text{–3}\text{1}\text{2}\text{hrs}$, after which time responding resumed at a reduced rate. When 0.25 mg naloxone HCl/kg was given during the recovery phase, the behavioral depressant effect of the narcotic was immediately reversed and operant performance returned to predrug rates. In contrast, when 0.5 mg naloxone/kg was given at this time, operant behavior was abolished for at least 1 hr. Naloxone, at these doses, did not affect responding in drug-naive subjects. These results suggest that a single, relatively low dose of morphine can induce transient dependence which is detectable for several hrs after drug administration, at a time when the acute pharmacological actions of morphine are still apparent.     

Anti-depressive-like effect of monoterpene trans-anethole via monoaminergic pathways

Trans-anethole (ANE) is a monoterpene present in many aromatic plants, especially Pimpinella anisum (PA). In this regard, we previously reported the anti-depressant potential of PA. Here, we examined the anti-depressant activity of ANE and its possible mechanism in mice. In experiment 1, the animals received ANE (12.5–50 mg.kg ^-1) 60 min prior to forced swimming and open-field tests. In experiment 2, the animals received several receptor antagonists to assess the possible mechanism of ANE. The administration of ANE (25 and 50 mg.kg ^-1; p < 0.01 and p < 0.001, respectively) exhibited an anti-depressive-like effect in FST without any significant effect on animal locomotion(p > 0.05). Moreover, haloperidol(p < 0.001), SCH23390(p < 0.001), sulpiride(p < 0.001), ketanserin(p < 0.001), p-chlorophenylalanine(p < 0.001), WAY100135(p < 0.001), reserpine, (p < 0.001) prazosin(p < 0.001), and yohimbine(p < 0.001) inhibited the anti-depressive-like effect of ANE. Furthermore, co-treatment of a subeffective dose of ANE with imipramine or fluoxetine induced synergistic anti-depressant-like effects(p < 0.001). Our data mainly showed that the anti-depressive-like effect of ANE, which can be attributed to the contribution of the monoaminergic system.     

The synthesis of NPY and DBH is independently regulated in adrenergic nerves after reserpine

A newly developed cytofluorimetric scanning technique was applied in a pharmacological study to investigate the influence of reserpine (10 mg/kg) on the axonal transport of norepinephrine (NE), dopamine--hydroxylase (DBH), tyrosine hydroxylase (TH), and neuropeptide Y (NPY)-like immunoreactivities (LI) in the adrenergic axons of the sciatic nerve of rat. Early after reserpine (18 hr and 24 hr after the reserpine injection) the amounts of NE accumulated proximal to a 12-hr crush werenil or very low, as observed in earlier studies. DBH-LI, TH-LI, and NPY-LI accumulations were also depressed but only to about 50% of control accumulations. This decrease in amounts of transported substances was probably caused by a decrease in protein synthesis and also a lowered velocity of fast axonal transport initially after reserpine, when body temperature is low. The amounts of accumulated NE, DBH-LI, TH-LI, and NPY-LI were normalized around day 2 after reserpine, but on day 4 NE, DBH-LI, and in some rats also TH-LI accumulated in supranormal amounts. However, NPY-LI accumulations were normal, indicating that DBH, butrot NPY, was trans- synaptically induced in rat sympathetic neurons, and that the biochemical composition of axonally transported organelles is altered for some days after reserpine.Dedicated to Dr. Abel Lajtha.     

Physical Activity and Low-Fat Diet: Is it Enough to Maintain Weight Stability in the Reduced-Obese Individual Following Weight Loss by Drug Therapy and Energy Restriction?

DOUCET, ERIC, PASCAL IMBEAULT, NATALIE ALMÉRAS, AND ANGELO TREMBLAY. Physical activity and low-fat diet: Is it enough to maintain weight stability in the reduced-obese individual following weight loss by drug therapy and energy restriction? Obes Res. Objective: The anthropometric and physiological effects of a physical activity (PA) and a mildly energy-restricted low-fat diet (LFD) follow-up program after a long-term dietary restriction were studied in 12 men and 8 women. Research Methods and Procedures: The dietary restriction (?700 kcal/day) was accompanied by a fenfluramine (60 mg/day) or placebo treatment for 15 weeks, whereas the mean duration of the PA-LFD follow-up was 18 weeks. Results: The long-term dietary restriction reduced body weight (?11. 9 and ?7. 6 kg, p<. 001), fat mass (FM) (?10. 6 and ?5. 8 kg, p<0. 01), resting metabolic rate (RMR) (?304 kcal/day, p<0. 01 and ?148 kcal/day, NS) in men and women, respectively. A decrease in fat-free mass (FFM) was also observed in women (?1. 8 kg, p<0. 05). The PA-LFD follow-up preserved weight stability at a reduced body weight and caused an additional significant decrease in FM for men (?3. 4 kg, p<0. 05). This part of the intervention also caused an increase in daily RMR for men (134 kcal/day, NS) to the point where this value no longer differed from the pre-energy restriction value. In contrast, RMR was further reduced in women (?200 kcal/day) to the point where it Significantly differed from initial values (p<0. 01). Resting seated heart rate was reduced by the PA-LFD follow-up in men leading it to differ significantly from both pre- and post-energy restriction values (?8. 5 and ?5. 5 bpm, p<0. 01). Discussion: In conclusion, these results suggest that a PA-LFD follow-up has the potential to permit body weight stability and may even accentuate fat loss in the reduced-obese state. Moreover, resting energy expenditure is increased under such conditions in men. These stimulating effects seem to be specific to energy metabolism since seated heart rate was either further reduced or remained stable in response to the PA-LFD follow-up.     

Inhibition of abstinence syndrome in opiate defendent mice by cyclo (His-Pro)

Intracerebral administration of cyclo (His-Pro), the postulated metabolite of thyroliberin (TRH, pGlu-His-Pro-NH₂) inhibited the naloxone induced withdrawal responses in morphine dependent mice. Mice were rendered dependent on morphine by the subcutaneous implantation of a pellet (containing 75 mg of morphine free base) for three days. Six hours after pellet removal, the naloxone ED₅₀ for the jumping response was found to be higher in mice injected with cyclo (His-Pro) compared with that of vehicle controls. Similarly, the hypothermic response observed following 50 μg/kg of naloxone given given 6 h after pellet removal or that seen with 100 μg/kg of naloxone given 24 h after pellet removal from morphine-dependent mice was inhibited by cyclo (His-Pro). Previously, we have shown similar results with TRH on the morphine abstinence syndrome. It appears, therefore, that cyclo (His-Pro) may be the active metabolite of TRH and analogs of cyclo (His-Pro) may be useful in blocking the symptoms of the opiate abstinence syndrome.