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Biomedical subjects

M Morag

Publications and source records attributed to M Morag.

At least 19 recordsLinked to original sources
PubMed2000

Illness, cytokines, and depression.

Various medical conditions that involve activation of the immune system are associated with psychological and neuroendocrine changes that resemble the characteristics of depression. In this review we present our recent studies, designed to investigate the relationship between the behavioral effects of immune activation and depressive symptomatology. In the first set of experiments, we used a double-blind prospective design to investigate the psychological consequences of illness in two models: (1) vaccination of teenage girls with live attenuated rubella virus, and (2) lipopolysaccharide (LPS) administration in healthy male volunteers. In the rubella study, we demonstrated that, compared to control group subjects and to their own baseline, a subgroup of vulnerable individuals (girls from low socioeconomic status) showed a significant virus-induced increase in depressed mood up to 10 weeks after vaccination. In an ongoing study on the effects of LPS, we demonstrated significant LPS-induced elevation in the levels of depression and anxiety as well as memory deficits. These psychological effects were highly correlated with the levels of LPS-induced cytokine secretion. In parallel experiments, we demonstrated in rodents that immune activation with various acute and chronic immune challenges induces a depressive-like syndrome, characterized by anhedonia, anorexia, body weight loss, and reduced locomotor, exploratory, and social behavior. Chronic treatment with antidepressants (imipramine or fluoxetine) attenuated many of the behavioral effects of LPS, as well as LPS-induced changes in body temperature, adrenocortical activation, hypothalamic serotonin release, and the expression of splenic TNF-alpha mRNA. Taken together, these findings suggest that cytokines are involved in the etiology and symptomatology of illness-associated depression.

Adolescent↗
PubMed1998

Influence of socioeconomic status on behavioral, emotional and cognitive effects of rubella vaccination: a prospective, double blind study.

A double-blind prospective design was used to investigate the immediate and prolonged psychological effects of a specific viral infection, and the role of immune activation in mediating these effects. Subjects were 240 female teenager girls who were vaccinated with rubella vaccine. Based on analysis of levels of antibodies to rubella, subjects were divided into two groups. An experimental group (n = 60), which included subjects who were initially seronegative and were infected following vaccination, and a control group (n = 180), which included subjects who were already immune to rubella before vaccination. Compared with the control group and to their own baseline, low socioeconomic status (SES) subjects within the experimental group showed a significant increase in the severity of depressed mood, social and attention problems, and delinquent behavior. Ten weeks post-vaccination there were no differences between the experimental and control groups in serum levels of interleukin-1 beta, interferon-gamma, soluble interleukin-2 receptors (sIL-2r), and cortisol. However, a significant negative correlation was found between fatigue-related symptoms and sIL-2r levels in the experimental (r = -0.325), but not the control group (r = -0.046). These findings suggest that viral infection can produce prolonged behavioral, emotional and cognitive problems mainly in subjects belonging to the low SES.

Adolescent↗
PubMed1984

Antiepileptic effects of amphetamine may require GABA (benzodiazepine) activity.

Secondary components of visual evoked potentials (slow negative wave-SNW, and photically-evoked sensory after discharge-SAD) are known to be precursors of experimentally activated wave-spike discharges, similar to wave-spikes of petit mal epilepsy. Both SNW and SAD may be potently suppressed either by amphetamine or GABAergic compounds such as diazepam and sodium valproate. A hypothesis was tested in the present study, that amphetamine-induced suppression of wave-spike discharges may require GABA-benzodiazepine activity for its expression. Electrocortical activity was recorded and averaged in unrestrained albino rats with chronically implanted epicortical electrodes. SNW and SAD obtained in habituated rats in the predrug state were potently suppressed by amphetamine (1 mg/kg, i.p.). Fifteen minutes after amphetamine injection, a challenging drug (metrazol, picrotoxin, convulsant benzodiazepine, Ro 5-3663, or imidazodiazepine, Ro 15-1788) was administered intraperitoneally. Subconvulsive doses of metrazol (10 mg/kg) reversed amphetamine suppression; imidazodiazepine (20 mg/kg) and picrotoxin (1.5 mg/kg) reliably opposed the SNW suppression; convulsant benzodiazepine, Ro 5-3663 (2 mg/kg), showed modest and nonsignificant effect in the same direction. It is proposed that the antiepileptic potency of amphetamine may be associated with its ability, apparently via modulatory effect of norepinephrine, to facilitate the activation of benzodiazepine-GABA receptors.

Amphetamine↗
PubMed1982

Benzodiazepine antagonists abolish electrophysiological effects of sodium valproate in the rat.

A hypothesis was considered that anti-epileptic potency of sodium valproate (VPA) may be associated with its action via the benzodiazepine system. The ability of anti-petit mal drugs to suppress the slow secondary negative wave (SNW) of the visually evoked potential was used as a sensitive electrophysiological "tag" for comparison of VPA (200 mg/kg, i.p.) and Diazepam (5 mg/kg, i.p.) effects. Both drugs induced a profound inhibition of the SNW. Benzodiazepine antagonists Ro 5-3663 (2 mg/kg, i.p.) and Ro 15-1788 (5 mg/kg, i.p.) caused recovery of the SNW amplitude within several minutes of injection. Both antagonists abolished immobility and sedation produced by VPA and Diazepam. The possibility should be considered that therapeutic effects of VPA are mediated through the benzodiazepine receptor coupled to GABA.

Animals↗
PubMed1981

Suppression by sodium valproate of gamma-vinyl GABA-induced facilitation of visual evoked potentials in rats.

A single dose (500 mg/kg, i.p.) of GABA-transaminase inhibitor, gamma-vinyl GABA (GVG), administered to Wistar rats caused time-related 2--3-fold enhancement of the slow negative wave (SNW) and sensory after-discharge (SAD) of the VEP. This effect was detectable at 1 h, reached plateau at 3--4 h and remained at this level 7 h after GVG. Sodium valproate (VPA, di-n-propylacetic acid), which is also believed to block GABA-transaminase and succinic semialdehyde dehydrogenase, when administered in a dose of 200 mg/kg (i.p.) 3 h after GVG reversibly antagonized the SNW-SAD hypersynchronization. The time-course of this effect was similar to that obtained after VPA administration alone. These findings are interpreted as suggesting that VPA acts via a mechanism using a transmitter intimately connected to but not identical with GABA.

4-Aminobutyrate Transaminase↗
PubMed1981

Pharmacologic analysis of sodium valproate-induced suppression of secondary components of visual evoked potentials in albino rats.

Sodium Valproate (VPA) administered to rats in a dose of 10 or 200 mg/kg IP suppressed the slow negative wave (SNW) and photically-induced afterdischarge (SAD) of VEP (when they were present) within 15-30 min. The recovery of VEP amplitude began at 3 hr. This effect was antagonized by subconvulsive doses of convulsant benzodiazepine RO 5-3663 (2 mg/kg) and metrazol (15 mg/kg) but not by picrotoxin (2 mg/kg) and naloxone (10 mg/kg). The SNW suppression may be attributed to a disinhibitory action of a system located presynaptically on recurrent collaterals of the output neurons, or nerve terminals of inhibitory interneurons or both. Alternative conjecture suggests that VPA depolarizes the dendritic tree masking thereby somatic inhibition produced by recurrent circuits.

Animals↗
PubMed1975

Effect of litter size on milk yield in the rat.

The amount of milk removed from rats during 1 hour's suckling after a separation period of 8 hours was estimated by weighing their pups. In the 1st experiment litters of 9 pups were suckled by all rats. At test sucklings held daily on days 6-15 of lactation, pups were reallocated to give 3, 6, 9, 12 or 15 pups per dam. The largest amount of milk was removed at suckling by groups of 12 pups. In a 2nd experiment, rats were constantly sucked by litters of either 3, 6, 9, 12 or 15 pups from birth to slaughter at 15 days post partum. Rats with 12 and 15 pups yielded the most milk, nearly twice as much as those suckling only 6 or 9 pups. Litters of 3 pups consumed less than 1/3 of the amount consumed by litters of 6 or 9 pups.

Animals↗