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M Weinstock

Publications and source records attributed to M Weinstock.

At least 19 recordsLinked to original sources
PubMed1992

Prenatal stress selectively alters the reactivity of the hypothalamic-pituitary adrenal system in the female rat.

A study was made of the effects of prenatal stress on the reactivity of the hypothalamic-pituitary adrenal (HPA) axis in male and female offspring. Rat dams were subjected to noise and light stress on an unpredictable basis throughout pregnancy. At 28 days of age mRNA for POMC, proenkephalin and prodynorphin were measured in the hypothalamus of the offspring. A marked reduction was found in POMC mRNA in PS females (PSF) but not in males (PSM), but the other mRNA's did not differ from controls (C). At 60 days of age, PSF has 3 times higher resting levels of serum corticosterone (COR) and significantly lower dexamethasone (DEX)3H hippocampal binding sites than CF. Overnight adrenalectomy abolished the difference in DEX binding. After 10 min exposure to open field PS males and females voided more fecal pellets and made fewer center entries than C offspring, testifying to increased emotionality. Open field stress caused a 3-5-fold rise in circulating COR in all groups within 15 min, which returned to baseline by 90 min in all rats except PSF. These data show that prenatal stress can cause permanent alterations in the behavior of both sexes in stressful situations but appears to cause a selective effect on the HPA axis in the female rat.

Animals↗
PubMed1992

Contrasting influences of central and peripheral opioids on cardiac baroreflex sensitivity in rabbits.

We studied the effects of naloxone [0.1 mg/kg intravenously (i.v.) or 7.5 micrograms/kg intracisternally (i.c.)], naloxone methyl iodide (NMI, 0.2 mg/kg, i.v. or 15 micrograms/kg i.c.) and morphine (2 mg/kg i.v.) on the cardiac baroreflex elicited in conscious rabbits especially bred for high and low baroreflex sensitivity (BRS) (group I, BRS > 5.5 beats/min/mm Hg and group II BRS < 4 beats/min/mm Hg, respectively). Full sigmoid barocurves were produced in 37 rabbits by i.v. injection of phenylephrine (1-15 micrograms/kg) and nitroglycerin (1-20 micrograms/kg) after pretreatment with saline or one of the above drugs. In group I, both naloxone i.v. and i.c. and NMI i.c. significantly reduced BRS and decreased the degree of bradycardia in response to a pressor stimulus; neither morphine nor NMI i.v. had any effect. In group II, naloxone i.v. and i.c. and NMI i.c. had no effect on BRS, but both morphine and NMI i.v. significantly increased BRS. An even greater increase was achieved by a combination of these drugs, which also increased specifically the degree of tachycardia in response to a decrease in blood pressure (BP). The results suggest that baroreceptor activation in group I released in the brainstem an opioid peptide that acts to increase BRS. In contrast, group II rabbits responded by peripheral opioid activation, which results in a decrease in BRS, possibly by inhibiting norepinephrine (NE) release from cardiac neurons. The predominance of peripheral or central opioid involvement in BRS modulation appears to be due to genetic factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Antagonism of morphine-induced respiratory depression by novel anticholinesterase agents.

This study compared the effects of 3 novel antiAChE agents (derivatives of dimethylaminoethyl-phenyl carbamate) with that of physostigmine on the respiratory depression induced by morphine in rabbits. Each drug, RA6, (1 mg i.v., 2 mg s.c.) RA7 (1 or 2 mg i.v.); RA15 (0.25 or 0.5 mg i.v.), physostigmine (0.05 or 0.1 mg i.v.) or saline (1 ml), was injected simultaneously with morphine (8 mg i.v.) to groups of 6-10 rabbits. Respiration rate, blood gases and pH were monitored for 3 hr. Plasma ChE was measured before and at 15 min intervals after injection. The 4 antiAChE's were given to 40 other rabbits, which were sacrificed at the time of maximal antagonism of the respiratory depressant effect of morphine, in order to measure the activity of AChE in the medulla, cortex and hippocampus. Physostigmine (0.1 mg) only antagonized the increase in paCO2 induced by morphine at 15 and 30 min. The drugs RA15 (0.5 mg), RA6 (2.5 mg) and RA7 (2 mg) almost completely prevented the respiratory depression, without obvious signs of peripheral cholinergic hyperactivity, for at least 3 hr. There was no relationship between the degree of antagonism of the effects of morphine with any drug and that of inhibition of ChE in plasma. In contrast, a highly significant correlation (P less than 0.01) was found between the former and the amount of inhibition of AChE in the medulla. It is suggested that the novel carbamates may have potential therapeutic application in reducing the respiratory depression of opiates, without impairing analgesia.

Acetylcholinesterase↗
PubMed1991

Relationship between baroreflex sensitivity, renin suppression and natriuresis in salt-sensitive rabbits.

This study determined the influence of baroreflex sensitivity (BRS) on the rate of urinary sodium excretion and plasma renin activity (PRA) in response to a saline infusion in conscious male rabbits specifically bred for high (Group I; n = 7) and low (Group II; n = 10) BRS and in seven control animals. Only Group II showed significant increases in blood pressure on a chronic high-salt intake. After ensuring that each animal was in sodium balance, a (0.7-0.9%) saline infusion of 3-4 ml/kg per h for 90 min (25% daily sodium intake for each rabbit) was given and urine collected at 15-min intervals via a bladder catheter. No differences were found in control urine volumes, urinary sodium or PRA. Group I excreted over 50% of the sodium load and Group II less than 20% within 90 min. PRA fell by more than 30% within 30 min in six Group I rabbits but decreased by less than 30% or increased in Group II. In the control animals, sodium excretion rates and PRA suppression were also much greater in those with high BRS. A highly significant correlation (r = 0.808, P less than 0.01) was found between the per cent of the sodium load excreted and BRS. It is suggested that the delayed sodium excretion and blood pressure elevation in salt-sensitive subjects may be due to a genetic impairment in baroreflex control of renal sympathetic nerve activity.

Animals↗
PubMed1990

Neonatal handling reverses behavioral abnormalities induced in rats by prenatal stress.

The aim of this study was to see whether neonatal handling can reverse the behavioral deficits induced in rats by unpredictable prenatal stress. Rats (24) were exposed to random noise and light stress (RS) on a random basis throughout pregnancy. Half the litters of RS and control (C) dams were subjected to neonatal handling (NH), 3' daily for 21 days. Behavioral measures, open field in both sexes and plus maze test in females only were conducted at 1.5-2 months, and spatial lateralization by amphetamine-induced rotation, in females at 3 months. RS caused significant increases in emotionality and timidity (higher incidence of defecation and less time in open arms of plus maze), and a change in directional bias towards the left. NH completely reversed all these behavioral abnormalities in RS rats but had little effect in C. It is concluded that NH can influence postnatal development of brain organisation in the opposite direction to that induced by prenatal stress.

Animals↗
PubMed1989

Alterations in behavioral and striatal dopamine asymmetries induced by prenatal stress.

We investigated the effects of maternal noise and light stress, randomly applied throughout pregnancy, on the development of behavioral and neurochemical asymmetries in the rat offspring. This form of maternal stress resulted in a rightward positioning of the tail of both sexes soon after birth as opposed to the leftward bias in controls. At adulthood, prenatally stressed offspring showed a change in directional bias compared to controls with a preponderance of left turns after amphetamine. In the males, this was expressed as a reduction in directional preference, while in females a reversal occurred of their dominant turning direction from right (controls) to left. We also observed a reduction in dopamine turnover rates in the left corpora striata of stressed offspring of both sexes. Again, in the females, this change was particularly marked and resulted in a reversal towards the right hemisphere. The findings from this study are consistent with the possibility that the alterations in cerebral asymmetries induced by prenatal stress may underly the decrease in the ability of the offspring to cope with anxiety provoking situations.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Opioid peptides mediate sympathetic inhibition in response to baroreceptor activation in a distinct genetic strain of rabbit.

1. Two strains of rabbits have been bred with marked differences in their cardiac baroreflex sensitivity (BRS). The difference in cardiac BRS was attenuated by naloxone. We compared the sympathetic responses to a pressor stimulus in these two strains, by measuring the changes in plasma catecholamines in the presence and absence of naloxone. 2. Cardiac BRS was assessed in eight rabbits of each group by the steady-state method. Two weeks later, both ear arteries and one ear vein were cannulated. Mean arterial pressure (MAP) and heart rate (HR) were recorded from one artery and blood samples (5 mL) for plasma catecholamines (CA) taken before, and during the peak of the pressor response to intravenous phenylephrine (PE, 20 micrograms/kg) from the other. The experiment was repeated 2-3 weeks later in rabbits with high BRS (Group I) after injection of naloxone 0.1 mg/kg, i.v. 3. Resting MAP and HR did not differ in the two groups. The mean gains of the cardiac baroreflex were 23.3 +/- 2.2 ms/mmHg in Group I and 6.3 +/- 1.1 ms/mmHg in Group II. After PE, MAP rose by 54.5 +/- 1.8 mmHg in Group II and 40.3 +/- 3.6 mmHg in Group I (P less than 0.02). The pressor response was associated with a 31% reduction in plasma noradrenaline (NA) in Group I and a 34% increase in Group II. The reduction in NA was significantly correlated with the degree of bradycardia in Group I (r = 0.72, P less than 0.05) and with BRS in both groups (r = 0.78, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Prenatal stress increases anxiety related behavior and alters cerebral lateralization of dopamine activity.

Effects of unpredictable (random) prenatal stress on the level of anxiety and cerebral lateralization of dopamine turnover rates were studied in rats. The observation of a decrease in the amount of time spent in the open arms of a "plus-maze" supported earlier findings of an increased fearfulness to stressful situations in the offspring in adulthood. We also observed elevated rates of dopamine turnover in the right prefrontal cortex and reduced dopamine activity in the right nucleus accumbens and left corpus striatum of the prenatally stressed animals. This resulted in directional shifts of left-right differences in dopamine activity in all 3 areas. These findings indicate that prenatal stress induces permanent alterations in dopaminergic activity and in cerebral asymmetry. We suggest that the changes in cerebral lateralization of dopamine function may underly the increase in reactivity to anxiety-provoking situations in prenatally stressed offspring.

Animals↗
PubMed1988

Differentiation of cardiac baroreflex properties by cuff and drug methods in two rabbit strains.

Sigmoidal mean arterial pressure (MAP)-heart rate (HR) curves were obtained in two genetically related strains of rabbits (groups I and II). We examined vagal (V) and sympathetic (S) effects on HR using perivascular cuffs and vasoactive drugs to alter MAP, and we studied the effects of intravenous naloxone, which affected only I. With the cuff method, both V and S components of gain were much greater in I than in II, and naloxone greatly reduced the difference. With the drug method, gain was similar in I and II and unaffected by naloxone. With both methods, the V component of HR range between plateaus was greater in I than in II because of more pronounced bradycardia at the lower plateau; naloxone eliminated the latter difference when the reflex was drug induced but not when it was cuff induced. The S component of HR range was similar in I and II; with both methods, the tachycardia plateau was reduced by naloxone. The cuff method alters cardiac load more than the drug method, leading to engagement of different groups of afferents for a given change in MAP (delta MAP). We have derived an input-output model, which suggests that with the drug method, gain is almost entirely determined by the input from the arterial baroreceptors, accounting for the minimal difference between I and II. With the cuff method, gain is determined by a nonlinear interaction involving the arterial and nonarterial baroreceptors, which accentuates the response. The opiate mechanism is associated with the nonarterial baroreceptor input and has amplifying properties, which account for the difference in gain between I and II. The two methods and naloxone provide a novel way of differentiating the effector patterns of the reflex; naloxone serves as a marker of activity in a particular pathway.

Animals↗
PubMed1988

[Hereditary resistance to salt-induced hypertension. What mechanisms?].

The Sabra hypertension resistant rats (SBN) have an outstanding ability to maintain normal blood pressure when exposed to procedures that ordinarily cause hypertension in normal rats. The following findings may be relevant to resistance to hypertension of these rats: 1) In SBN rats, cardiac norepinephrine content is not affected by DOCA-salt treatment. Since depletion of cardiac norepinephrine is an index of cardiac adrenergic nerve overactivity, the results suggest an attenuated cardiac sympathetic nerve activity in these rats. 2) In SBN rats, the sensitivity of the baroreflex control of the heart is markedly increased compared with other strains. Reduction of baro-receptor sensitivity by aortic-baroreceptor deafferentation renders them susceptible to DOCA-salt hypertension. The results suggest a strong relationship between baroreflex supersensitivity and resistance to hypertension in these rats. 3) The amount of alpha 2 adrenoreceptor densities in cerebral and renal cortical membranes of normal rats increased in vitro, in the presence of sodium and guanyl nucleotide (GTP). In SBN rats, the effect of sodium is markedly attenuated compared with SBH, while response to GTP is identical in the two strains. The demonstration of a similar pattern of response in the Dahl rats suggests that alpha 2 adrenoreceptor may be involved in the sensitivity or resistance to salt induced hypertension.

Animals↗
PubMed1987

Increased interhemispheric coupling of the dopamine systems induced by prenatal stress.

Maternal noise and light stress, randomly applied throughout pregnancy, has previously been shown to induce alterations in behavioral asymmetries in the adult offspring. In the present study, we investigated whether interhemispheric communication of neurotransmitters would be influenced by this treatment. Dopamine and serotonin turnover rates were measured in the left and right prefrontal cortex, nucleus accumbens and caudate nucleus of adult rats which were stressed prenatally. In control animals, dopamine turnover was only significantly correlated between the left and right hemispheres in the males (p less than 0.01). Prenatal stress greatly increased the degree of interhemispheric correlation (p less than 0.001) which now became highly significant in both sexes (p less than 0.001). For serotonin, left-right turnover rates only correlated in control females and no effect of gestational stress was seen. These results indicate that prenatal stress greatly increases interhemispheric coupling of dopamine in the adult offspring. We suggest that this facilitated communication may underly the alterations in behavioral asymmetries induced by prenatal stress.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Temporal factors influencing the development of acute tolerance to opiates.

The present study investigated the influence of the extent of drug effect, duration of action and dose interval on the development of acute tolerance to the respiratory and cardiovascular depressant effects of opiates. Morphine (2, 4 and 10 mg/kg i.v.) caused a dose-related reduction in heart and respiratory rates and elevation in PaCO2 which lasted 4 to 4.5 hr. Acute tolerance occurred to the effect of a second dose of 4 or 10 mg/kg but not 2 mg/kg given 4 hr after the first. When the duration of action of the opiate was limited to 75 min by injection of naloxone (0.125 mg/kg) or by the use of a short acting opiate, fentanyl (0.025 mg/kg), tolerance to a second dose of drug still developed provided it was given at least 4 hr later. When naloxone was given at the peak of the morphine effect (30 min) tolerance did not occur. It is concluded that the development of acute tolerance to opiates depends on the degree of initial drug effect and the time of receptor occupancy. The latter must be longer than that required to attain a peak response. A time period of about 4 hr appears to be necessary for the full development of the biochemical processes involved in this phenomenon.

Animals↗
PubMed1986

Effects of prenatal stress on vulnerability to stress in prepubertal and adult rats.

This study investigated the hypotheses that unpredictable prenatal stress has effects on the offspring, similar to those induced by perinatal administration of glucocorticoids and increases the vulnerability to stressful situations at adulthood. Rats were exposed to random noise and light stress throughout pregnancy. Offspring were tested for the development of spontaneous alternation behavior (SA) and at adulthood, their response to novel or aversive situations, open field, extinction and punishment following acquisition of an appetitive response and two-way active avoidance, were assessed. In prenatally stressed rats, the development of SA was significantly delayed. On repeated exposure to an open field they were less active; control rats had elevated plasma corticosterone (CCS) on days 2 and 4 of open field exposure, while prenatally stressed rats had significantly raised plasma CCS after each exposure (days 1-8). Furthermore, punishment-induced suppression of an appetitive response was enhanced. Acquisition of active avoidance was faciliated in female but reduced in male prenatally stressed offspring. It is suggested that random prenatal noise and light stress may cause impairment of development of hippocampal function which lasts into adulthood. This impairment is manifested as an increase in vulnerability and a decrease in habituation to stressful stimuli.

Animals↗
PubMed1986

Are the effects of gestational stress on motor development and cerebellar cholinesterase activity mediated prenatally?

Prenatal random noise and light stress retards early motor development in the rat. To determine whether this delay is pre- or postnatally mediated and whether the developing cerebellum may play a role in the delay, rats were subjected to this form of stress and their offspring were fostered or cross-fostered onto control rats and vice versa. Their motor development was assessed by a series of behavioral tests between birth and day 10 of life. Prenatally stressed pups (Eo), whether reared by stressed (Em) or control mothers (Cm), showed a retardation in motor development. However, stressed pups matured earlier when reared by a control mother than by a stressed dam. Control pups (Co) raised by stressed mothers showed normal behavioral development. Cerebellar cholinesterase activity, which has been shown to undergo characteristic alterations with normal maturation, did not differ between stressed and control pups at birth. However, on day 10, cholinesterase activity was lower in EmCo than in CmCo pups, whereas that in CmEo and EmEo pups did not differ significantly from controls. It is concluded that three effects of random noise and light stress during pregnancy may be distinguished: (1) A prenatal effect as expressed by a delay in motor development, (2) a postnatal (rearing) effect on motor development and (3) a rearing effect expressed as a decrease in cerebellar ChE activity.

Animals↗
PubMed1986

Mechanism of antagonism by physostigmine of acute flunitrazepam intoxication.

The effect of physostigmine on the loss of consciousness and respiratory depression induced in rabbits by flunitrazepam, 1 mg/kg, was studied to demonstrate whether the restoration of consciousness and respiration rate results from an increase in central cholinergic activity or from an interference by physostigmine with specific binding of flunitrazepam to its receptors. Physostigmine, 0.1-0.4 mg/kg iv, caused a dose-related reversal of consciousness and respiration rate within 15 min of its injection, which lasted 15-30 min depending on the dose. This was associated with peak inhibition of acetylcholinesterase (AChE) in the frontal cortex and medulla, at 15 min, ranging from 35-51%. The analeptic effect of physostigmine in flunitrazepam-treated rabbits was prevented by pretreatment with scopolamine, 1 mg/kg. The effective dose range for physostigmine, 3-12 mumol/kg, is close to concentrations of this agent that inhibit activity in solubilized preparations of AChE from rabbit cortex, 1-3 X 10(-8) M. However, physostigmine, 10(-9) -10(-4) M, failed to displace 3H flunitrazepam from specific binding sites on membranes prepared from rabbit cerebral cortex. It is concluded that physostigmine antagonizes the somnolence and respiratory depression induced by benzodiazepines by restoring cholinergic transmission to normal levels. The effective dose range of physostigmine is small, and serious side effects from overdose can occur as a result of excess cholinergic activity at neuromuscular synapses.

Acetylcholinesterase↗
PubMed1986

Pharmacological evaluation of an injectable prolonged release emulsion of physostigmine in rabbits.

Physostigmine was incorporated in an injectable emulsion in an attempt to prolong its pharmacological activity. Emulsions which remained stable over 6 month storage were prepared using optimal experimental conditions. The in-vitro kinetic examination revealed that the rate-determining step in the release process of physostigmine from the emulsion was its partitioning from the oily phase to the external aqueous phase. The in-vivo results indicated that the physostigmine emulsion was able to inhibit the cholinesterase activity for only 1 to 2 h. The preliminary pharmacokinetic analysis showed that the physostigmine emulsion apparently increased the bioavailability compared with the conventional injectable solution. This could be attributed either to the protection of the sensitive drug from the enzymatic degradation or to improved absorption. The presence of poloxamer micelles in the aqueous phase was shown to enhance the bioavailability of physostigmine without having any effect on its pharmacological activity or duration.

Acetylcholinesterase↗